Patent Publication Number: US-2010113297-A1

Title: Method for predicting the occurrence of metastasis in breast cancer patients

Description:
FIELD OF THE INVENTION 
     The present invention relates to the prognosis of the progression of breast cancer in a patient, and more particularly to the prediction of the occurrence of metastasis in one or more tissue or organ of patients affected with a breast cancer. 
     BACKGROUND OF THE INVENTION 
     Breast cancer is the most common malignant disease in Western women. It is not the primary tumour, but the occurrence of metastases in distant organs that is the major cause of death for cancer patients. Once solid secondary tumours are established, the chances of long-term survival fall from 90% to around 5%. Despite the progress in the development of targeted therapies, approximately 40% of the treated patients relapse and ultimately die of metastatic breast cancer. A better understanding of the molecular and cellular mechanisms underlying metastasis might improve the development of effective therapies that would ameliorate breast cancer care. 
     Malignant breast tumours can invade and damage nearby tissues and organs. Malignant tumour cells may metastasise, entering the bloodstream or lymphatic system. When breast cancer cells metastasise outside the breast, they are often found in the lymph nodes under the arm (axillary lymph nodes). If the cancer has reached these nodes, it means that cancer cells may have spread to other lymph nodes or other organs, such as bones, liver, brain or lungs. Breast cancer metastasis of various organs also occurs without previous spreading to lymph nodes. Major and intensive research has been focussed on early detection, treatment and prevention of metastatic breast cancer. 
     The rational development of preventive, diagnostic and therapeutic strategies for women at risk for breast cancer would be aided by a molecular map of the tumorigenesis process. Relatively little is known of the molecular events that mediate the transition of normal breast cells to the various stages of breast cancer progression. Similarly, little is known of the molecular events that mediate the transition of cells from one stage of breast cancer to another, and finally to metastasis. 
     Molecular means of identifying the differences between normal, non-cancerous cells and cancerous cells have been the focus of intense study. The use of cDNA libraries to analyse differences in gene expression patterns in normal versus tumourigenic cells has been described. Gene expression patterns in human breast cancers have been described by Perou et al. (1999, Proc. Natl. Acad. Sci. USA, Vol. 96: 9212-9217), who studied gene expression between cultured human “normal” mammary epithelia cells (HMEC) and breast tissue samples by using microarrays comprising about 5000 genes. They used a clustering algorithm to identify differential patterns of expression in HMEC and tissue samples. Perou et al. (2000, Nature, Vol. 406: 747-752) described the use of clustered gene expression profiles to classify subtypes of human breast tumours. Hedenfalk et al. (2001, New Engl. J. Medicine, Vol. 344(8): 539-548) described gene expression profiles in BRCA1 mutation positive, BRCA2 mutation positive, and sporadic tumours. Using gene expression patterns to distinguish breast tumour subclasses and predict clinical implications is described by Sorlie et al. (2001, Proc. Natl. Acad. Sci USA, Vol. 98(19): 10869-10874) and West et al. (2001, Proc. Natl. Acad. Sci USA, Vol. 98(20): 11462-11467). 
     Based on the assumption that primary tumours may already contain genes that are predictive of metastastatic process, several groups performed genome wide microarray studies to identify expression profiles associated with the occurrence of distant relapses and poor survival. Several highly prognostic gene signatures were reported containing genes potentially involved in metastatic processes and/or markers of distant relapses. These studies mainly tackled overall relapses problems. 
     Searches aimed at identifying biological markers that would be involved in breast cancer metastasis in several tissues or organs have also been performed in the art. For this purpose, in vivo experiments using human breast cancer xenographs in nude mice were performed, as described below. 
     Kang et al. (2003, Cancer Cell, Vol. 3: 537-549) identified a set of genes potentially involved in breast cancer metastasis to bone, by comparing (i) the gene expression profile obtained from in vitro cultured cells of the MDBA-MB-231 human breast cancer cell line with (ii) the gene expression profile obtained from a subclone of the same cell line previously experimentally selected in vivo for their ability to form bone metastasis in mice. Using microarray gene expression analysis techniques, these authors showed that several genes were underexpressed and several other genes were overexpressed in the cell sublines selected for their ability to form bone metastasis in mice, as compared to the parental MDBA-MB-231 human breast cancer cell line. These authors concluded that, in the case of the human MDA-MB-231 cell line, cell functions that are relevant for metastasis to bone might be carried out by CXCR4, CTGF, IL-11 and OPN genes, with possible contributions of other genes. 
     Minn et al. (2005, Nature, Vol. 436(28): 518-524) used the same human parental MDA-MB-231 breast cancer cell line for selecting in vivo cell sublines having the ability to form lung metastasis in mice. Then, these authors have performed a transcriptomic microarray analysis of the highly and weakly lung-metastatic cell populations, with the view of identifying patterns of gene expression that would be associated with aggressive lung metastatic behaviour. A final list of 54 candidate lung metastagenicity and virulence genes was selected, twelve of them having been further identified for their significant association with lung-metastasis-free survival, including MMP1, CXCL1 and PTGS2. 
     In the studies reported above, the authors identified and functionally validated a set of genes that specifically mediate bone or lung metastasis in the animal model. The organ-specific gene signatures that were identified allowed to distinguish between (i) primary breast carcinomas that preferentially metastasized to bone or lung from (ii) those that metastasized elsewhere. 
     One study recently reported a molecular signature allowing for an bone-specific metastasis prognosis of human breast cancer. This work was performed by comparing primary breast tumors relapsing to bone to those relapsing elsewhere. The authors thereby identified a panel of genes associated to breast cancer metastasis to bone (Smid et al., 2006, J Clin Oncol, Vol. 24(15):2261-2267). 
     However, testing the organ-specific signature on mixed cohort of primary tumors did not allow robust classification of those tumors that gave rise to specific metastases versus those that did not. This is probably due to little predictive value of these gene signatures. 
     An early detection of metastasis in breast cancer patients is crucial for adapting the anti-cancer therapeutic treatment correspondingly, with the view of increasing the chances of long term disease-free survival. 
     However, because detection of metastasis in breast cancer patients, even if the said detection is performed at an early stage of metastasis, consists of a poor prognosis of the cancer outcome, there is an increasing need in the art for the availability of reliable methods for detecting the metastasis potentiality of a breast cancer tumour, for both medical treatment and medical survey purposes. There is also a need in the art for methods that would provide a prediction of the one or more tissues or organs in which the formation and development of a breast cancer metastasis would be likely to occur. 
     SUMMARY OF THE INVENTION 
     The present invention relates to methods and kits for predicting the occurrence of metastasis in patients affected with a breast cancer. 
     The breast cancer metastasis prediction methods of the invention comprise a step of determining, in a tumour tissue sample previously collected from a breast cancer patient to be tested the level of expression of one or more biological markers that are indicative of cancer progression towards metastasis, and more precisely, one or more biological markers that are indicative of cancer progression towards metastasis to specific tissues, and especially to bones, brain, lungs and liver. 
     This invention also relates to breast cancer metastasis prediction kits that are specifically designed for performing the metastasis prediction methods above. 
     This invention also pertains to methods for selecting one or more biological markers that are indicative of cancer progression towards metastasis in specific tissues, including bones, brain, lungs and liver. 
    
    
     
       BRIEF DESCRIPTION OF THE FIGURES 
         FIG. 1 : Test of the bone and lung metastatic associated genes on primary tumors. Hierarchical clustering of relapsing primary breast carcinomas from a cohort of 27 patients was performed with the lung (A) and bone (B) metastatic signatures. Lung-metastasis-free survival and bone-metastasis-free survival analysis of corresponding patients was performed. Tumors from patients A2 (bottom line) express lung metastatic associated genes in a manner resembling lung relapses. Tumors from patients B2 (bottom line line) express bone metastatic associated genes in a manner resembling bone relapses. 
         FIG. 2 : Segregation of primary breast carcinomas using the organ-specific signature.  FIG. 2A  depicts lung metastasis-free survival.  FIG. 2B  depicts bone metastasis-free survival.  FIG. 2C  depicts overall metastasis-free survival. Lung-metastasis-free survival (Kaplan Meier analysis) for 82 breast cancer patients who either expressed ( FIG. 2A , corresponding to cluster A) or did not express (green line) the lung metastasis signature (cluster B+C). 
         FIG. 3 : Performance of the six-gene lung metastasis signature in a series of 72 node-negative breast tumors (the CRH cohort) (A) Distribution of distant metastases (first and/or only metastatic sites) in the high-risk and low-risk groups identified by the six-gene signature (Chi 2  test). (B) Patients with tumors expressing the six-gene signature (high-risk group) had shorter lung-metastasis-free survival (log-rank test). (C and D) Kaplan-Meier curves of bone-metastasis-free survival and liver metastasis-free survival showed no difference between the high- and low-risk groups identified by the six-gene signature. 
         FIG. 4 : Validation of the six-gene lung metastasis signature in 3 independent series of breast cancer patients. Lung-metastasis-free survival was analyzed for MSK ( FIG. 4A ), EMC ( FIG. 4B ) and NKI ( FIG. 4C ) cohorts (82, 344 and 295 patients respectively) and the combined cohort of 721 breast cancer patients ( FIG. 4D ). Kaplan-Meier analysis distinguished patients who expressed (high-risk group) and did not express (low-risk group) the six-gene signature. Patients with a high predicted risk of lung metastasis had shorter lung-metastasis-free survival. 
         FIG. 5 : Integration of diverse clinicopathological markers and gene expression signatures for lung metastasis risk prediction. (A) Prediction of breast cancer lung metastasis is improved by using a combination of predictors derived from 2 distinct models. (B) Distribution of lung metastases in the combined cohort of 721 breast cancer patients (MSK/EMC/NKI) according to the clinically and experimentally derived signatures. Patients that are negative for both signatures are shown in black; those with divergent assignement are indicated in blue; and patients found positive for both signatures are shown in green. The six-gene and LMS signatures showed 85% agreement in outcome classification of breast cancer patients with respect to lung metastasis (Kappa coefficient=0.57). (B) Kaplan-Meier analysis of breast cancer patients (n=721) according to the six-gene and MDA-derived lung metastasis signatures. 
         FIG. 6 : Test of bone metastatic associated genes on primary tumors: Hierarchical clustering of relapsing primary breast carcinomas from a cohort of patients was performed with the eleven-gene bone metastatic signature. Bone metsatsis-free survival analysis of corresponding patients was performed. 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     Methods allowing an early prediction of the likelihood of development of metastasis in breast cancer patients are provided by the present invention. 
     Particularly, it is provided herein methods and kits allowing prediction of the occurrence of metastasis to one or more specific tissue or organ in breast cancer patients, notably in bone, lung, liver and brain tissues or organs. 
     According to the present invention, highly reliable tissue-specific sets of biological markers that are indicative of a high probability of metastasis occurrence in breast cancer patients have been identified. 
     The identification of these highly reliable tissue-specific sets of biological markers was permitted, due to the use of a highly accurate method for the screening of such metastasis biological markers that is described below in the present specification. 
     Thus, an object of the present invention consists of an in vitro method for predicting the occurrence of metastasis in a patient affected with a breast cancer, comprising the steps of:
         a) providing a breast tumour tissue sample previously collected from the patient to be tested;   b) determining, in the said breast tumour tissue sample, the expression of one or more biological markers that are indicative of an occurrence of metastasis in one or more tissue or organ, wherein the said one or more biological markers are selected from the group consisting of:
           (i) one or more biological markers indicative of an occurrence of metastasis in the bone tissue that are selected from the group consisting of: CLEC4A, MFNG, NXF1, FAM78A, KCTD1, BAIAP2L1, PTPN22, MEGF10, PERP, PSTPIP1, FLI1, COL6A2, CD4, CFD, ZFHX1B, CD33, LST1, MMRN2, SH2D3C, RAMPS, FAM26B, ILK, TM6SF1, C10orf54, CLEC3B, IL2RG, HOM-TES-103, ZNF23, STK35, TNFAIP8L2, RAMP2, ENG, ACRBP, TBC1D10C, C11orf48, EBNA1BP2, HSPE1, GAS6, HCK, SLC2A5, RASA3, ZNF57, WASPIP, KCNK1, GPSM3, ADCY4, A1F1, NCKAP1, AMICA1, POP7, GMFG, PPM1M, CDGAP, GIMAP1, ARHGAP9, APOB48R, OCIAD2, FLRT2, P2RY8, RIPK4, PECAM1, URP2, BTK, APBB1IP, CD37, STARD8, GIMAP6, E2F6, WAS, HLA-DQB1, HVCN1, L0056902, ORC5L, MEF2C, PLCL2, PLAC9, RAC2, SYNE1, DPEP2, MYEF2, HSPD1, PSCD4, NXT1, LOC340061, ITGB3, AP1S2, SNRPG, CSF1, BIN2, ANKRD47, LIMS2, DARC, PTPN7, MSH6, GGTA1, LRRC33, GDPD5, CALC0001, FAM110C, BCL6B, LOC641700, ARHGDIB, DAAM2, TNFRSF14, TPSAB1, CSF2RA, RCSD1, FLJ21438, LOC133874, GSN, SLIT3, FYN, NCF4, PTPRC, EVI2B, SCRIB, C11orf31, LOC440731, TFAM, ARPC5L, PARVG, GRN, LMO2, CRSP8, EHBP1L1, HEATR2, NAALADL1, LTB, STRBP, FAM65A, ADARB1, TMEM140, DENND1C, PRPF19, CASP10, SLC37A2, RHOJ, MPHOSPH10, PPIH, RASSF1, HCST, C16orf54, EPB41L4B, LRMP, LAPTM5, PRDM2, CYGB, LYCAT, ACP5, CMKLR1, UBE1L, MAN2C1, TNFSF12, C7orf24, Cxorf15, CUL1, SMAD7, ITGB7, APOL3, PGRMC1, PPA1, YES1, FBLN1, MRC2, PTK9L, LRP1, IGFBP5, WDR3, GTPBP4, SPI1, SELPLG, OSCAR, LYL1, POLR2H, YWHAQ, ISG20L2, LGI14, KIF5B, NGRN, TYROBP, C5orf4, COX7A2, S100A4, MATK, TMEM33, DOK3, LOC150166, CIRBP, NIN, C10orf72, FMNL1, FATS, CHKB/CPT1B, SNRPA1, GIMAP4, C20orf18, LTBP2, GABS, NQO1, MARCH2, MYO1F, CDS1, SRD5A1, C20orf160, SLAMF7, ACTL6A, ABP1, RAE1, MAF, SEMA3G, P2RY13, ZDHHC7, ERG, CLEC10A, INTS5, MYO15B, CTSW, PILRA, HN1, SCARA5, PRAM1, EBP, SIGLEC9, LGP1, DGUOK, GGCX, RABL5, ZBTB16, NOP5/NOP58, CCND2, CD200, EPPK1, DKFZp586C0721, CCT6A, RIPK3, ARHGAP25, GNAI2, USP4, FAHD2A, LOC399959, LOC133308, HKDC1, CD93, GTF3C4, ITGB2, ELOVL6, TGFB111, ASCC3L1, FES, AACS, ATP6VOD2, TMEM97, NUDT15, ATP6V1B2, CCDC86, FLJ10154, SCARF2, PRELP, ACHE, GIMAP8, PDE4DIP, NKG7, C20orf59, RHOG, TRPV2, TCP1, TNRC8, TNS1, IBSP, MMP9, NRIP2, OLFML2B, OMD, WIF1, ZEB2, ARL8, COL12A1, EBF and EBF3;   (ii) one or more biological markers indicative of an occurrence of metastasis in the lung tissue that are selected from the group consisting of: SC2, HORMAD1, PLEKHG4, ODF2L, C21orf91, TFCP2L1, TTMA, CHODL, CALB2, UGT8, LOC146795, C1orf210, SIKE, ITGB8, PAQR3, ANP32E, C20orf42/FERMT1, ELAC1, GYLTL1B, SPSB1, CHRM3, PTEN, PIGL, CHRM3, CDH3;   (iii) one or more biological markers indicative of an occurrence of metastasis in the liver tissue that are selected from the group consisting of: TBX3, SYT17, LOC90355, AGXT2L1, LETM2, LOC145820, ZNF44, IL20RA, ZMAT1, MYRIP, WHSC1L1, SELT, GATA2, ARPC2, CAB39L, SLCI6A3, DHFRL1, PRRT3, CYP3A5, RPS6KA5, KIAA1505, ATP5S, ZFYVE16, KIAA0701, PEBP1, DDHD2, WWP1, CCNL1, ROBO2, FAM111B, THRAP2, CRSP9, KARCA1, SLC16A3, ARID4A, TCEAL1, SCAMP1, KIAAO701, EIF5A, DDX46, PEX7, BCL2L11, YBX1, UBE21, REXO2, AXUD1, C10orf2, ZNF548, FBXL16, LOC439911, LOC283874, ZNF587, FLJ20366, KIAAO888, BAG4, CALU, KIAA1961, USP30, NR4A2, FOXA1, FBXO15, WNK4, CDIPT, NUDT16L1, SMAD5, STXBP4, TTC6, LOC113386TSPYL1, CIP29, C8orf1SYDE2, SLC12A8, SLC25A18, C7, STAU2, TSC22D2, GADD45G, PHF3, TNRC6C, TCEAL3, RRN3, C5orf24, AHCTF1, LOC92497; and   (iv) one or more biological markers indicative of an occurrence of metastasis in the brain tissue that are selected from the group consisting of: LOC644215, BAT1, GPR75, PPWD1, INHA, PDGFRA, MLL5, RPS23, ANTXR1, ARRDC3, PTK2, SQSTM1, METTL7A, NPHP3, PKP2, DDX31, FAM119A, LLGL2, DDX27, TRA16, HOXB13, GNAS, CSPP1, COL8A1, RSHL1, DCBLD2, UBXD8, SURF2, ZNF655, RAC3, AP4M1, HEG1, PCBP2, SLC30A7, ATAD3A/ATAD3B, CHI3L1, MUC6, HMG20B, BCL7A, GGN, ARHGEF3, PALLD, TOP1, PCTK1, C20orf4, ZBTB1, MSH6, SETD5, POSTN, MOCS3, GABPA, ZSWIM1, ZNHIT2, LOC653352, ELL, ARPC4, ZNF277, VAV2, HNRPH3, LHX1, FAM83A, DIP2B, RBM10, PMPCA, TYSND1, RAB4B, DLC1, KIAA2018, TES, TFDP2, C3orf10, ZBTB38, PSMD7, RECK, JMJD1C, F1120273, CENPB, PLAC2, C6orf111, ATP10D, RNF146, XRRA1, NPAS2, APBA2BP, WDR34, SLK, SBF2, SON, MORC3, C3orf63, WDR54, STX7, ZNF512, KLHL9, LOC284889, ETV4, RMND5B, ARMCX1, SLC29A4, TRIB3, LRRC23, DDIT3, THUMPD3, MICAL-L2, PA2G4, TSEN54, LAS1L, MEA1, S100PBP, TRAF2, EMILIN3, KIAA1712, PRPF6, CHD9, JMJD1B, ANKS1A, CAPN5, EPC2, WBSCR27, CYB561, LLGL1, EDD1.   
           c) predicting the occurrence of metastasis in one or more tissue or organ when one or more of the said biological markers has (have) a deregulated expression level, as compared to its corresponding expression level measured in a breast tumour sample of a patient that has not undergone metastasis in the corresponding tissue or organ.       

     As previously mentioned herein, prior art studies disclosed several gene signatures containing genes potentially involved in metastatic processes and/or markers of distant relapses. However, these prior art studies tackled overall relapses problems. As there are multiple types of metastases and potentially multiple distinct pathological processes leading to metastases, these prior art studies suffered for lack of accuracy. 
     Notably, according to a plurality of these prior art methods, selection of metastasis-specific biological markers was performed by human marker expression analysis in artificial in vivo systems, namely in non-human animals, especially in mice. 
     Further, the screening of metastasis-specific biological markers were generally performed using artificial human cell systems, namely established human cancer cell lines, wherein expression artefacts of one or more genes or proteins cannot be excluded. The probability of introduction of biological markers expression artefacts was further increased by various features of the screening methods which were used, including the selection of multiple human cell sublines having a metastatic potency derived from the parental cell line, by reiterating in vivo cycles of cell administration/selection in non-human animal systems, including mice. 
     Still further, according to these prior art techniques, once pertinent cell sublines were finally selected for their high metastatic potency in non-human animals, differential gene expression analysis was performed by comparing the expression levels of genes between (i) the parental human breast cancer cell line and (ii) the various cell sublines having a metastatic potency. 
     In view of improving the accuracy of the prior art techniques of selecting metastasis-specific markers for breast cancer, the inventors have designed an original method for selecting highly reliable tissue-specific biological markers of metastasis in breast cancer, using a whole human system of analysis and including, among other features, a step of comparing the expression level of candidate biological markers between (i) a metastatic tissue or organ of interest and (ii) one or more distinct metastatic tissue(s) or organ(s), thus allowing a high selectivity and statistical relevance of the tissue-specific metastatic biological markers that are positively selected, at the end of the marker selection method. 
     As it is shown in the examples herein, when using a marker selection method comprising a step of comparing the expression level of candidate biological markers between (i) a metastatic tissue or organ of interest selected from the group consisting of bone, lung, liver and brain and (ii) all the other metastatic tissue(s) or organ(s) selected from the group consisting of bone, lung, liver and brain, the inventors have identified tissue-specific breast cancer metastasis biological markers endowed with a high statistical relevance, with P values always lower than 1.10 −4 , the said P values being lower than 10 −6  for the most statistically relevant biological markers. Statistical relevancy of the biological markers primarily selected was fully corroborated by Kaplan-Meier analysis, after having assayed for the expression of the said tissue-specific markers in tumour tissue samples of breast cancer patients, as it is shown in the examples herein. 
     As intended herein; a “biological marker” encompasses any detectable product that is synthesized upon the expression of a specific gene, and thus includes gene-specific mRNA, cDNA and protein. 
     As used herein, a “biological marker indicative of an occurrence of metastasis”, or a “metastasis-specific marker”, encompasses any biological marker which is differentially expressed in breast tumors that generate metastasis, or will generate metastasis, in a specific given tissue or in a specific given organ, as compared to the expression of the same biological marker in breast tumors that do not generate metastasis, or will not generate metastasis, in the said specific given tissue or in the said specific given organ. Preferably, tissues and organs are selected from the group consisting of bone, lung, liver and brain. 
     The terms “tissue-specific” marker and “tissue metastasis-specific” marker are used interchangeably herein. Similarly, the terms “organ-specific” marker and “organ metastasis-specific” marker are used interchangeably herein. 
     As intended herein, a “prediction of the occurrence of metastasis” does not consist of an absolute value, but in contrast consists of a relative value allowing to quantify the probability of occurrence of a metastasis to one or more specific tissue(s) or organ(s), in a breast cancer patient. In certain embodiments, the prediction of the occurrence of metastasis is expressed as a statistical value, including a P value, as calculated from the expression values obtained for each of the one or more biological markers that have been tested. 
     As intended herein, a “tumour tissue sample” encompasses (i) a global primary tumour (as a whole), (ii) a tissue sample from the center of the tumour, (iii) a tissue sample from a location in the tumour, other than the center of the tumour and (iv) any tumor cell located outside the tumor tissue per se. In certain embodiments, the said tumour tissue sample originates from a surgical act of tumour resection performed on the breast cancer patient. In certain other embodiments, the said tissue sample originates from a biopsy surgical act wherein a piece of tumour tissue is collected from the breast cancer patient for further analysis. In further embodiments, the said tumor sample consists of a blood sample, including a whole blood sample, a serum sample and a plasma sample, containing tumour cells originating from the primary tumor tissue, or alternatively from metastasis that have already occurred. In still further embodiments, the said tumor sample consists of a blood sample, including a whole blood sample, a serum sample and a plasma sample, containing tumor proteins produced by tumor cells originating from the primary tumor tissue, or alternatively from metastasis that have already occurred. 
     The various biological markers names specified herein correspond to their internationally recognised acronyms that are usable to get access to their complete amino acid and nucleic acid sequences, including their complementary DNA (cDNA) and genomic DNA (gDNA) sequences. Illustratively, the corresponding amino acid and nucleic acid sequences of each of the biological markers specified herein may be retrieved, on the basis of their acronym names, that are also termed herein “gene symbols”, in the GenBank or EMBL sequence databases. All gene symbols listed in the present specification correspond to the GenBank nomenclature. Their DNA (cDNA and gDNA) sequences, as well as their amino acid sequences are thus fully avaialble to the one skilled in the art from the GenBank database, notably at the following Website address: “http://www.ncbi.nlm.nih.gov/”. The same sequences may also be retrieved from the Hugo Gene Nomenclature Committee (HGCN) database that is available at the following Website address: http://www.gene.ucl.ac.uk/nomenclature/. 
     At step b) of the in vitro prediction method according to the invention, one or more of the specified biological markers is (are) quantified. Quantification of a biological marker includes detection of the expression level of the said biological marker. Detection of the expression level of a specific biological marker encompasses the assessment of the amount of the corresponding specific mRNA or cDNA that is expressed in the tumour tissue sample tested, as well as the assessment of the amount of the corresponding protein that is produced in the said tumour tissue sample. 
     At the end of step b) of the method according to the invention, a quantification value is obtained for each of the one or more biological markers that are used. 
     As it has been previously specified, specific embodiments of step b) include:
         (i) quantifying one or more biological markers by immunochemical methods, which encompasses quantification of one or more protein markers of interest by in situ immunohistochemical methods on a tumor tissue sample, for example using antibodies directed specifically against each of the said one or more protein markers.   (ii) quantifying one or more biological markers by gene expression analysis, which encompasses quantification of one or more marker mRNAs of interest, for example by performing a Real-Time PCR Taqman PCR analysis, as well as by using specifically dedicated DNA microarrays, i.e. DNA microarrays comprising a substrate onto which are bound nucleic acids that specifically hybridize with the cDNA corresponding to every one of the biological markers of interest, among the biological markers listed herein.       

     In certain other embodiments of the method, step b) consists of quantifying, in a tumor tissue sample, the expression level of one or more marker genes among those specified above. Generally, the assessment of the expression level for a combination of at least two marker genes is performed. In these embodiments of step b) of the method, what is obtained at the end of step b) consists of the expression level values found for each marker gene (nucleic acid or protein expression level) specifically found in cells contained in the tumour tissue sample. 
     The expression level of a metastasis-specific biological marker according to the present invention may be expressed as any arbitrary unit that reflects the amount of the corresponding mRNA of interest that has been detected in the tissue sample, such as intensity of a radioactive or of a fluorescence signal emitted by the cDNA material generated by PCR analysis of the mRNA content of the tissue sample, including (i) by Real-time PCR analysis of the mRNA content of the tissue sample and (ii) hybridization of the amplified nucleic acids to DNA microarrays. Preferably, the said expression level value consists of a normalised relative value which is obtained after comparison of the absolute expression level value with a control value, the said control value consisting of the expression level value of a gene having the same expression level value in any breast tissue sample, regardless of whether it consists of normal or tumour breast tissue, and/or regardless whether it consists of a non-metastatic or a metastatic breast tissue. Illustratively, the said control value may consist of the amount of mRNA encoding the TATA-box-binding protein (TBP), as it is shown in the examples herein. 
     Alternatively, the said expression level may be expressed as any arbitrary unit that reflects the amount of the protein of interest that has been detected in the tissue sample, such as intensity of a radioactive or of a fluorescence signal emitted by a labelled antibody specifically bound to the protein of interest. Alternatively, the value obtained at the end of step b) may consist of a concentration of protein(s) of interest that could be measured by various protein detection methods well known in the art, such as. ELISA, SELDI-TOF, FACS or Western blotting. 
     Because every one of the biological markers that are specified herein consists of a biological marker (i) that is specifically expressed, including at a given expression level, exclusively in a given breast cancer metastatic tissue or organ and (ii) that is expressed at another expression level, in a distinct breast cancer metastatic tissue or organ, then the sole quantification of its expression in a tumour tissue sample originating from a primary tumour specimen allows to predict whether the breast cancer-bearing patient is likely to undergo generation of metastasis in the said tissue or organ. 
     Additionally, quantifying the said one or more biological markers that are specified herein brings further prediction data relating to the probability of occurrence of metastasis in one or more specific tissue or organ in a breast cancer-bearing patient, since the probability of occurrence of metastasis increases with an increased deregulation of the expression level of the said one or more biological markers tested, as compared to their control expression level that is previously measured in a breast tumor sample from a patient that has not undergone metastasis, at least in the tissue or organ of interest that is considered. 
     Thus, as used herein, a biological marker of interest having a “deregulated expression level” consists of a metastasis-specific biological marker for which is found, when performing step b) of the in vitro prediction method according to the invention, an expression level value that is distinct from the expression level value (that may also be termed the “control” expression value) for the said biological marker that has been previously determined (i) in tumor tissue samples originating from breast cancer patients that have never undergone metastasis, or alternatively (ii) in tumor tissue samples originating from breast cancer patients that have never undergone metastasis in the tissue or organ from which the said biological marker is metastasis-specific. For performing step c) of the prediction method according to the invention, the one skilled in the art may refer to the deregulated expression values for each of the metsatasis-specific markers described herein, as they are found notably in Tables 1, 2, 5 and 8. 
     As it is shown in the examples, every one of the biological markers listed herein is highly relevant for predicting the occurrence of metastasis in a specific tissue, since the markers having the lowest statistical relevance possess a P value lower than 1.10 −4 . 
     Further, accuracy of the metastasis prediction increases, at step c) of the method, when more than one tissue-specific biological marker for a given tissue or organ is detected and/or quantified at step b). 
     Thus, in preferred embodiments of the prediction method according to the invention, more than one biological marker for a given tissue or organ is detected and/or quantified, at step b) of the method. 
     The more biological markers specific for a given tissue or organ are quantified at step b) of the method, the more accurate are the prediction results that are obtained at step c) of the said method. 
     Quantifying a plurality of biological markers specific for a given tissue or organ at step b) of the method allows to generate an experimental expression profile of the said plurality of markers, which expreimental expression profile is then compared with at least one reference expression profile that has been previously determined from tissue-specific metastasis patients. Illustratively, if bone metastasis is suspected in the patient tested, then the experimental expression profile that is generated from the results of quantification of the bone metastasis-specific marker genes used at step b) of the method is compared with the pre-existing reference expression profile corresponding to bone metastasis, for prediction. Preferably, the experimental expression profile of the bone-specific metastasis markers is compared with reference expression profiles of the same genes that have been previously determined in patients having bone metastasis, as well as with reference expression profiles obtained from patients having other tissue- or organ-specific metastasis, so as to ensure that the experimental expression profile is the most close from the reference expression profile predetermined from patients having bone metastasis. 
     In certain embodiments of the prediction method, step b) comprises quantifying at least one tissue-specific biological marker for each tissue or organ. Illustratively, in those embodiments of the method, step b) comprises quantifying (i) at least one bone-specific biological marker, (ii) at least one lung-specific biological marker, (iii) at least one liver-specific biological marker and (iv) at least one brain-specific biological marker. 
     In certain embodiments of the method, step b) comprises quantifying at least two tissue-specific biological markers for a given tissue or organ. The higher the number of tissue-specific markers for a given tissue or organ are quantified at step b), the more accurate is the prediction of occurrence of metastasis in the said given tissue in the breast cancer-bearing patient tested. 
     Thus, in certain embodiments of the prediction method according to the invention, the number of biological markers tested for a given tissue or organ is of at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199; 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299 or 300 distinct tissue-specific biological markers for a given tissue or organ selected from the group consisting of the tissue-biological markers disclosed in the present specification, the maximum number of distinct tissue-specific biological markers for a given tissue or organ being limited by the number of markers that are disclosed herein for the said given tissue or organ. 
     Any combination of two or more of the biological marker described herein is fully encompassed by the present invention. 
     When a plurality of biological markers for each of the tissues or organs are quantified, at step b) of the method, then experimental expression profiles of the patient tested may be generated, that are then compared to the reference expression profiles of the same biological markers, so as to determine to which reference expression profile the experimental expression profile is the most similar, and thus which tisue- or organ-specific metastasis may eventually be predicted. 
     In some embodiments of the prediction method according to the invention, step c) may be performed by the one skilled in the art by calculating a risk index of organ-specific metastasis of the patient tested, starting from the expression level values of the one or more biological markers that ave been determined at step b). Numerous methods for calculating a risk index are well known from the one skilled in the art. 
     Illustratively, the one skilled in the art may calculate the risk index of the patient tested, wherein the said risk index is defined as a linear combination of weighted (or not, depending one the genes tested) expression level values with the standardized Cox&#39;s regression coefficient as the weight.    
     
       
         
           
             
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               A 
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     wherein:
         A is a constant   w i  is the standardized Cox&#39;s regression coefficient for the markers   x i  is the expression value of the marker (log scale)   n is the number of genes to predict the risk       

     The threshold is determined from the ROC curve of the training set to ensure the highest sensitivity and specificity. The constant value A is chosen to center the threshold of the risk index to zero. Patients with positive risk index are classified into the high risk of organ-specific group and patients with negative risk index are classified into the low risk of organ-specific group. 
     Illustrative embodiments of the prediction method according to the invention, wherein step c) is performed by calculating a risk index of organ-specific metastasis of the patient tested are illustrated in Tables 9, 10, 11 and 12. 
     Table 9 illustrates the predictive values of various lung-specific biological markers that may be used in the method according to the invention. 
     Details of Table 9 are given hereunder. 
     Cohort: EMC-344 TP 
     Summary of Results:
         Number of genes significant at 0.99 level of the univariate test: 23   Genes significantly associated with survival:   Table 9—Sorted by p-value of the univariate test.   The first 23 genes are significant at the nominal 0.99 level of the univariate test   Hazard ratio is the ratio of hazards for a two-fold change in the gene expression level.   It is equal to exp(b) where b is the Cox regression coefficient. SD is the standard deviation of the log 2 of the gene expression level.
 
Table 10 illustrates the predictive values of various lung-specific biological markers that may be used in the method according to the invention. Details of Table 10 are given hereunder.
       

     Cohort: MSK-82 TP 
     Summary of Results:
         Number of genes significant at 0.99 level of the univariate test: 23   Genes significantly associated with survival:   Table 10—Sorted by p-value of the univariate test.   The first 23 genes are significant at the nominal 0.99 level of the univariate test   Hazard ratio is the ratio of hazards for a two-fold change in the gene expression level.2 of the gene expression level.   It is equal to exp(b) where b is the Cox regression coefficient. SD is the standard deviation of the log
 
Table 11 illustrates the predictive values of various lung-specific biological markers that may be used in the method according to the invention. Details of Table 11 are given hereunder.
       

     Cohort: NKI-295 
     Summary of Results:
         Number of genes significant at 0.9 level of the univariate test: 20   Genes significantly associated with survival:   Table 11—Sorted by p-value of the univariate test.   The first 20 genes are significant at the nominal 0.9 level of the univariate test   Hazard ratio is the ratio of hazards for a two-fold change in the gene expression level. 2 of the gene expression level.   It is equal to exp(b) where b is the Cox regression coefficient. SD is the standard deviation of the log 2 of the gene expression level.
 
Table 12 illustrates the predictive values of various bone-specific biological markers that may be used in the method according to the invention. Details of Table 12 are given hereunder.
       

     Cohort: NKI-295 
     Summary of Results:
         Number of genes significant at 0.99 level of the univariate test: 51   Genes significantly associated with survival:   Table 1—Sorted by p-value of the univariate test.   The first 51 genes are significant at the nominal 0.99 level of the univariate test   Hazard ratio is the ratio of hazards for a two-fold change in the gene expression level.   It is equal to exp(b) where b is the Cox regression coefficient. SD is the standard deviation of the log 2 of the gene expression level.       

     Also, the 40 highest ranking bone-specific biological markers that have been identified according to the present invention are shown in Table 13 hereunder. 
     In certain embodiments of the prediction method according to the invention, the one or more bone-specific biological markers that are quantified at step b) are selected from the group consisting of CLEC4A, MFNG, NXF1, FAM78A, KCTD1, BAIAP2L1, PTPN22, MEGF10, PERP, PSTPIP1, FL11, COL6A2, CD4, CFD, ZFHX1B, CD33, MMRN2, LST1, SH2D3C and RAMPS. Those bone-specific markers possess a high statistical relevance for predicting the occurrence of metastasis in bone tissue, with P values obtained after DNA microarray analysis that are always lower than 10 −6 , as shown in Table 2 
     In certain embodiments of the prediction method according to the invention, the one or more lung-specific biological markers that are quantified at step b) are selected from the group consisting of DSC2, HORMAD1, PLEKHG4, ODF2L, c21orf91, TFCP2L1, CHODL, CALB2, UGT8, c1orf210, SIKE, ITGB8, PAQR3, ANP32E, KIND1, ELAC1, GYLTL1B, SPSB1, PTEN and CHRM3. Those lung-specific markers possess a high statistical relevance for predicting the occurrence of metastasis in lung tissue or organ, with P values obtained after DNA microarray analysis that are always lower than 10 −4 , as shown in Table 2 
     In certain embodiments of the prediction method according to the invention, the one or more liver-specific biological markers that are quantified at step b) are selected from the group consisting of TBX3, c5orf30, AGXT2L1, LETM2, ZNF44, IL20RA, ZMAT1, MYRIP, WHSC1L1, SELT, GATA2, DHFRL1, ARPC2, SLC16A3, GNPTG, PRRT3, RPS6KA5, K1 AA1505, ZFYVE16 and K1AA0701. Those liver-specific markers possess a high statistical relevance for predicting the occurrence of metastasis in liver tissue or organ, with P values obtained after DNA microarray analysis that are always lower than 10 −5 , as shown in Table 2 
     In certain embodiments of the prediction method according to the invention, the one or more brain-specific biological markers that are quantified at step b) are selected from the group consisting of PPWD1, INHA, PDGFRA, MLL5, RPS23, ANTXR1, ARRDC3, METTL7A, NPHP3, PKP2, DDX27, TRA16, HOXB13, CSPP1, RSHL1, DCBLD2, UBXD8, SURF2, ZNF655 and RAC3. Those brain-specific markers possess a high statistical relevance for predicting the occurrence of metastasis in brain tissue or organ, with P values obtained after DNA microarray analysis that are always equal to, or lower than, 10 −5 , as shown in Table 2. 
     In certain other embodiments of the prediction method according to the invention, the one or more tissue-specific biological markers are selected from the following groups of markers:
         (i) the group of bone metastasis-specific markers consisting of KTCD1, BAIAP2L1, PERP, CFD, CD4, COL6A2, FLI1, PSTPIP1, MGF10, PTPN22, FAM78A, NXF1, MFNG and CLEC4A;   (ii) the group of lung metastasis-specific markers consisting of KIND1, ELAC1, ANP32E, PAQR3, ITGB8, c1orf210, SIKE, UGT8, CALB2, CHODL, c21orf91, TFCP2L1, ODF2L, HORMAD1, PLEKHG4 and DSC2;   (iii) the group of liver metastasis-specific makers consisting of GATA2, SELT, WHSC1L1, MYRIP, ZMAT1, IL20RA, ZNF44, LETM2, AGXT2L1, c5orf30 and TBX3.   (iv) the group of brain metastasis-specific markers consisting of PPWD1, PDGFRA, MLL5, RPS23, ANTXR1, ARRDC3, METTL7A, NPHP3, RSHL1, CSPP1, HOXB13, TRA16, DDX27, PKP2 and INHA.       

     In still other embodiments of the prediction method according to the invention, the one or more tissue-specific biological markers are selected from the following groups of markers:
         (i) the group of bone metastasis-specific markers consisting of BAIAP2L1, PERP, CFD, CD4, COL6A2, FLI1, PSTPIP1, MGF10, PTPN22, FAM78A, NXF1, MFNG and CLEC4A;   (ii) the group of lung metastasis-specific markers consisting of KIND1, ANP32E, ITGB8, UGT8, TFCP2L1, HORMAD1 and DSC2;   (iii) the group of liver metastasis-specific makers consisting of GATA2, WHSC1L1, LETM2, AGXT2L1 and TBX3.   (iv) the group of brain metastasis-specific markers consisting of PPWD1, PDGFRA, ANTXR1, ARRDC3 and DDX27.       

     In yet further embodiments of the prediction method according to the invention, the one or more lung-specific biological markers that are detected and/or quantified at step b) are selected from the group consisting of DSC2, TFCP2L1, UGT8, ITGB8, ANP32E and FERMT1. 
     In still further embodiments of the prediction method according to the invention, the one or more bone-specific biological markers that are detected and/or quantified at step b) are selected from the group consisting of KCNK1, CLEC4A, MFNG, NXF1, PTPN22, PERP, PSTPIP1, FL11, COL6A2, CD4 and CFD. Predictive results of these bone-specific biological markers are shown in Table 8 hereunder. 
     As it is shown in examples 3 to 6 herein, the said lung-specific markers possess a high statistical relevance for predicting the occurrence of metastasis in lung tissue or organ, with P values obtained after DNA microarray analysis that are always lower than 10 −4 , as shown notably in Table 5. 
     The lung-specific markers DSC2, TFCP2L1, UGT8, ITGB8, ANP32E and FERMT1 are all up-regulated in individuals affected with breast cancer and bearing lung metastasis, as compared with breast cancer patients who have no lung metastasis or with individuals who are not affected with a breast cancer, as shown in Table 5. 
     As shown in examples 3 to 6 herein, the DSC2, TFCP2L1, UGT8, ITGB8, ANP32E and FERMT1 lung-specific markers consists of a six-gene signature which is predictive of selective breast cancer relapse to the lungs. 
     As shown in the examples herein, this six-gene signature (DSC2, TFCP2L1, UGT8, ITGB8, ANP32E and FERMT1) was generated from a series of lymph node-negative breast cancer patients who did not receive any neoadjuvant or adjuvant therapy to allow the analysis of the signature prognostic impact along with the natural history of the disease. The predictor would thus not be influenced by factors related to systemic treatment. 
     This six-gene signature was validated in three independent cohort of breast cancers consisting of a total of 721 patients, as detailed hereafter and as illustrated in the examples herein. The said six-gene signature was thus validated in two independent data sets of patients of early stage (n=295 and 344) generated from two distinct microarray platforms and a third series of locally advanced breast cancer patients (n=82). In all tested individual series and in the combined cohort (n=721), the six gene signature had a strong predictive ability for breast cancer lung metastasis. 
     The results described in the examples herein show that the said six-gene signature improves risk stratification independently of known standard clinical parameters and previously established lung metastasis signature based on an experimental model. 
     Although there is no targeted therapy for lung metastasis, such as bisphosphonates for bone metastasis, the knowledge of organ-specific metastasis has been emphasized the last few years and might lead to targeted therapeutics in the near future. By delineating the risk for lung metastasis based on gene signatures, it might be possible that these high-risk breast cancer patients may benefit from these therapies targeting specific secondary failures. 
     Thus, in a further embodiment of the prediction method according to the invention, step b) consists of determining, in the breast tumour tissue sample, the expression of one or more biological markers that are indicative of an occurrence of metastasis in the lung tissue that are selected from the group consisting of DSC2, TFCP2L1, UGT8, ITGB8, ANP32E and FERMT1. 
     In the above-embodiment of the prediction method according to the invention, the expression of 2, 3, 4, 5 or all of the six lung-specific markers is determined, i.e. detected end/or quantified. 
     In certain embodiments of the prediction method according to the invention, every one of the tissue-specific biological markers comprised in each group of markers disclosed herein is submitted to quantification. In those embodiments, step b) comprises quantifying every biological marker contained in each group of markers disclosed herein. More precisely, according to those embodiments of the method, step b) comprises quantifying every biological marker contained in (i) one group of bone-specific markers, (ii) one group of lung-specific markers, (iii) one group of liver-specific markers and (iv) one group of brain-specific markers, selected among the various groups of (i) bone-specific markers, (ii) lung-specific markers, (iii) liver-specific markers and (iv) brain-specific markers disclosed in the present specification. 
     Indeed, the use of every possible combination of at least two metastasis-specific biological markers, that are selected from the group consisting of all the metastasis-specific biological markers disclosed in the present specification, is encompassed herein, for the purpose of performing the in vitro prediction method according to the invention. 
     Preferably, the use of every possible combination of four or more metastasis-specific biological markers, provided that each possible combination comprises (i) one or more bone metastasis-specific biological marker, (ii) one or more lung metastasis-specific biological marker, (iii) one or more liver metastasis-specific biological marker and (iv) one or more liver metastasis-specific biological marker, is encompassed herein, for the purpose of performing the in vitro prediction method according to the invention. 
     Thus, in certain embodiments of the prediction method according to the invention, at least one biological marker selected from each of the groups (i), (ii), (iii) and (iv) is quantified at step b). 
     In certain embodiments of the prediction method, all biological markers from specific groups (i), (ii), (iii) and (iv) are quantified at step b). 
     Thus, in certain embodiments of the prediction method according to the invention, step b) consists of determining (i.e. detecting and/or quantifying), in the breast tumour tissue sample, the expression of every one of the following lung-specific markers: DSC2, TFCP2L1, UGT8, ITGB8, ANP32E and FERMT1. 
     Also, in certain embodiments of the prediction method according to the invention, step b) consists of determining (i.e. detecting and/or quantifying), in the breast tumor sample, the expression of every one of the following bone-specific markers: KCNK1, CLEC4A, MFNG, NXF1, PTPN22, PERP, PSTPIP1, FL11, COL6A2, CD4 and CFD. 
     At step b), the said one or more biological markers may be quantified by submitting the said breast tumour tissue sample to a gene expression analysis method. 
     At step b), the said one or more biological markers may alternatively be quantified by submitting the said breast tumour tissue sample to an immunohistochemical analysis method. 
     General methods for quantifying the tissue-specific biological markers disclosed herein are detailed below. 
     General methods for quantifying biological markers 
     Any one of the methods known by the one skilled in the art for quantifying a protein biological marker or a nucleic acid biological marker encompassed herein may be used for performing the metastasis prediction method of the invention. Thus any one of the standard and non-standard (emerging) techniques well known in the art for detecting and quantifying a protein or a nucleic acid in a sample can readily be applied. 
     Such techniques include detection and quantification of nucleic acid biological markers with nucleic probes or primers. 
     Such techniques also include detection and quantification of protein biological markers with any type of ligand molecule that specifically binds thereto, including nucleic acids (e.g. nucleic acids selected for binding through the well known Selex method), and antibodies including antibody fragments. In certain embodiments wherein the biological marker of interest consists of an enzyme, these detection and quantification methods may also include detection and quantification of the corresponding enzyme activity. 
     Noticeably, antibodies are presently already available for most, if not all, the biological markers described in the present specification, including those biological markers that are listed in Table 4 
     Further, in situations wherein no antibody is yet available for a given biological marker, or in situations wherein the production of further antibodies to a given biological marker is sought, then antibodies directed against the said given biological markers may be easily obtained with the conventional techniques, including generation of antibody-producing hybridomas. In this method, a protein or peptide comprising the entirety or a segment of a biological marker protein is synthesised or isolated (e.g. by purification from a cell in which it is expressed or by transcription and translation of a nucleic acid encoding the protein or peptide in vivo or in vitro using known methods). A vertebrate, preferably a mammal such as a mouse, rat, rabbit, or sheep, is immunised using the protein or peptide. The vertebrate may optionally (and preferably) be immunised at least one additional time with the protein or peptide, so that the vertebrate exhibits a robust immune response to the protein or peptide. Splenocytes are isolated from the immunised vertebrate and fused with an immortalised cell line to form hybridomas, using any of a variety of methods well known in the art. Hybridomas formed in this manner are then screened using standard methods to identify one or more hybridomas which produce an antibody which specifically binds with the biological marker protein or a fragment thereof. The invention also encompasses hybridomas made by this method and antibodies made using such hybridomas. Polyclonal antibodies may be used as well. 
     Expression of a tissue-specific biological marker described herein may be assessed by any one of a wide variety of well known methods for detecting expression of a transcribed nucleic acid or protein. Non-limiting examples of such methods include immunological methods for detection of secreted, cell-surface, cytoplasmic, or nuclear proteins, protein purification methods, protein function or activity assays, nucleic acid hybridisation methods, nucleic acid reverse transcription methods, and nucleic acid amplification methods. 
     In one preferred embodiment, expression of a marker is assessed using an antibody (e.g. a radio-labelled, chromophore-labelled, fluorophore-labeled, polymer-backbone-antibody, or enzyme-labelled antibody), an antibody derivative (e.g. an antibody conjugated with a substrate or with the protein or ligand of a protein-ligand pair {e.g. biotin-streptavidin}), or an antibody fragment (e.g. a single-chain antibody, an isolated antibody hypervariable domain, etc.) which binds specifically with a marker protein or fragment thereof, including a marker protein which has undergone all or a portion of its normal post-translational modification. 
     In another preferred embodiment, expression of a marker is assessed by preparing mRNA/cDNA (i.e. a transcribed polynucleotide) from cells in a patient tumour tissue sample, and by hybridising the mRNA/cDNA with a reference polynucleotide which is a complement of a marker nucleic acid, or a fragment thereof. cDNA can, optionally, be amplified using any of a variety of polymerase chain reaction methods prior to hybridisation with the reference polynucleotide. 
     In a preferred embodiment of the in vitro prediction method according to the invention, step b) of detection and/or quantification of the one or more biological markers is performed using DNA microarrays. Illustratively, according to this preferred embodiment, a mixture of transcribed polynucleotides obtained from the sample is contacted with a substrate having fixed thereto a polynucleotide complementary to or homologous with at least a portion (e.g. at least 7, 10, 15, 20, 25, 30, 40, 50, 100, 500, or more nucleotide residues) of a biological marker nucleic acid. If polynucleotides complementary to or homologous with are differentially detectable on the substrate (e.g. detectable using different chromophores or fluorophores, or fixed to different selected positions), then the levels of expression of a plurality of markers can be assessed simultaneously using a single substrate (e.g. a “gene chip” microarray of polynucleotides fixed at selected positions). When a method of assessing marker expression is used which involves hybridisation of one nucleic acid with another, it is preferred that the hybridisation be performed under stringent hybridisation conditions. 
     An exemplary method for detecting and/or quantifying a biological marker protein or nucleic acid in a tumour tissue sample involves obtaining a tumour tissue sample. Said method includes further steps of contacting the biological sample with a compound or an agent capable of detecting the polypeptide or nucleic acid (e.g., mRNA or cDNA). The detection methods of the invention can thus be used to detect mRNA, protein, or cDNA, for example, in a tumour tissue sample in vitro. For example, in vitro techniques for detection of mRNA include Northern hybridisation and in situ hybridisation. In vitro techniques for detection of a biological marker protein include enzyme linked immunosorbent assays (ELISAs), Western blots, immunoprecipitations, immunofluorescence, and RT-PCR. A general principle of such detection and/or quantification assays involves preparing a sample or reaction mixture that may contain a biological marker, and a probe, under appropriate conditions and for a time sufficient to allow the marker and probe to interact and bind, thus forming a complex that can be removed and/or detected in the reaction mixture. 
     As used herein, the term “probe” refers to any molecule which is capable of selectively binding to a specifically intended target molecule, for example, a nucleotide transcript or protein encoded by or corresponding to a biological marker. Probes can be either synthesised by one skilled in the art, or derived from appropriate biological preparations. For purposes of detection of the target molecule, probes may be specifically designed to be labelled, as described herein. Examples of molecules that can be utilised as probes include, but are not limited to, RNA, DNA, proteins, antibodies, and organic molecules. 
     These detection and/or quantification assays of a biological marker can be conducted in a variety of ways. 
     For example, one method to conduct such an assay would involve anchoring the probe onto a solid phase support, also referred to as a substrate, and detecting target marker/probe complexes anchored on the solid phase at the end of the reaction. In one embodiment of such a method, a sample from a subject, which is to be assayed for quantification of the biological marker, can be anchored onto a carrier or solid phase support. In another embodiment, the reverse situation is possible, in which the probe can be anchored to a solid phase and a sample from a subject can be allowed to react as an unanchored component of the assay. 
     There are many established methods for anchoring assay components to a solid phase. These include, without limitation, marker or probe molecules which are immobilised through conjugation of biotin and streptavidin. Such biotinylated assay components can be prepared from biotin-NHS (N-hydroxy-succinimide) using techniques known in the art (e.g., biotinylation kit, Pierce Chemicals, Rockford, Ill.), and immobilised in the wells of streptavidin-coated 96 well plates (Pierce Chemical). In certain embodiments, the surfaces with immobilised assay components can be prepared in advance and stored. 
     Other suitable carriers or solid phase supports for such assays include any material capable of binding the class of molecule to which the marker or probe belongs. Well-known supports or carriers include, but are not limited to, glass, polystyrene, nylon, polypropylene, nylon, polyethylene, dextran, amylases, natural and modified celluloses, polyacrylamides, gabbros, and magnetite. 
     In order to conduct assays with the above mentioned approaches, the non-immobilised component is added to the solid phase upon which the second component is anchored. After the reaction is complete, uncomplexed components may be removed (e.g., by washing) under conditions such that any complexes formed will remain immobilised upon the solid phase. The detection of marker/probe complexes anchored to the solid phase can be accomplished in a number of methods outlined herein. 
     In a preferred embodiment, the probe, when it is the unanchored assay component, can be labelled for the purpose of detection and readout of the assay, either directly or indirectly, with detectable labels discussed herein and which are well-known to one skilled in the art. 
     It is also possible to directly detect marker/probe complex formation without further manipulation or labelling of either component (marker or probe), for example by utilising the technique of fluorescence energy transfer (see, for example, Lakowicz et al., U.S. Pat. No. 5,631,169; Stavrianopoulos, et al., U.S. Pat. No. 4,868,103). A fluorophore label on the first, ‘donor’ molecule is selected such that, upon excitation with incident light of appropriate wavelength, its emitted fluorescent energy will be absorbed by a fluorescent label on a second ‘acceptor’ molecule, which in turn is able to fluoresce due to the absorbed energy. Alternately, the ‘donor’ protein molecule may simply utilize the natural fluorescent energy of tryptophan residues. Labels are chosen that emit different wavelengths of light, such that the ‘acceptor’ molecule label may be differentiated from that of the ‘donor’. Since the efficiency of energy transfer between the labels is related to the distance separating the molecules, spatial relationships between the molecules can be assessed. In a situation in which binding occurs between the molecules, the fluorescent emission of the ‘acceptor’ molecule label in the assay should be maximal. A FRET binding event can be conveniently measured through standard fluorometric detection means well known in the art (e.g., using a fluorimeter). 
     In another embodiment, determination of the ability of a probe to recognise a marker can be accomplished without labelling either assay component (probe or marker) by utilising a technology such as real-time Biomolecular Interaction Analysis (BIA) (see, e.g., Sjolander, S. and Urbaniczky, C., 1991, Anal. Chem. 63:2338-2345 and Szabo et al., 1995, Curr. Opin. Struct. Biol. 5:699-705). As used herein, “BIA” or “surface plasmon resonance” is a technology for studying biospecific interactions in real time, without labelling any of the interactants (e.g., BIAcore). Changes in the mass at the binding surface (indicative of a binding event) result in alterations of the refractive index of light near the surface (the optical phenomenon of surface plasmon resonance (SPR)), resulting in a detectable signal which can be used as an indication of real-time reactions between biological molecules. 
     Alternatively, in another embodiment, analogous diagnostic and prognostic assays can be conducted with marker and probe as solutes in a liquid phase. In such an assay, the complexed marker and probe are separated from uncomplexed components by any of a number of standard techniques, including but not limited to: differential centrifugation, chromatography, electrophoresis and immunoprecipitation. In differential centrifugation, marker/probe complexes may be separated from uncomplexed assay components through a series of centrifugal steps, due to the different sedimentation equilibria of complexes based on their different sizes and densities (see, for example, Rivas, G., and Minton, A. P., 1993, Trends Biochem Sci. 18(8):284-7). Standard chromatographic techniques may also be utilized to separate complexed molecules from uncomplexed ones. For example, gel filtration chromatography separates molecules based on size, and through the utilization of an appropriate gel filtration resin in a column format, for example, the relatively larger complex may be separated from the relatively smaller uncomplexed components. Similarly, the relatively different charge properties of the marker/probe complex as compared to the uncomplexed components may be exploited to differentiate the complex from uncomplexed components, for example through the utilization of ion-exchange chromatography resins. Such resins and chromatographic techniques are well known to one skilled in the art (see, e.g., Heegaard, N. H., 1998, J. Mol. Recognit. Winter 11(1-6):141-8; Hage, D. S., and Tweed, S. A. J Chromatogr B Biomed Sci Appl 1997 Oct. 10; 699(1-2):499-525). Gel electrophoresis may also be employed to separate complexed assay components from unbound components (see, e.g., Ausubel et al., ed., Current Protocols in Molecular Biology, John Wiley &amp; Sons, New York, 1987-1999). In this technique, protein or nucleic acid complexes are separated based on size or charge, for example. In order to maintain the binding interaction during the electrophoretic process, non-denaturing gel matrix materials and conditions in the absence of reducing agent are typically preferred. SELDI-TOF technique may also be employed on matrix or beads coupled with active surface, or not, or antibody coated surface, or beads. 
     Appropriate conditions to the particular assay and components thereof will be well known to one skilled in the art. 
     In a particular embodiment, the level of marker mRNA can be determined both by in situ and by in vitro formats in a biological sample using methods known in the art. The term “biological sample” is intended to include tissues, cells, biological fluids and isolates thereof, isolated from a subject, as well as tissues, cells and fluids present within a subject, provided that the said biological sample is susceptible to contain (i) cells originating from the breast cancer or (ii) nucleic acids or proteins that are produced by the breast cancer cells from the patient. Many expression detection methods use isolated RNA. For in vitro methods, any RNA isolation technique that does not select against the isolation of mRNA can be utilised for the purification of RNA from breast cancer (see, e.g., Ausubel et al., ed., Current Protocols in Molecular Biology, John Wiley &amp; Sons, New York 1987-1999). Additionally, large numbers of tissue samples can readily be processed using techniques well known to those of skill in the art, such as, for example, the single-step RNA isolation process of Chomczynski (1989, U.S. Pat. No. 4,843,155). 
     The isolated mRNA can be used in hybridisation or amplification assays that include, but are not limited to, Southern or Northern analyses, polymerase chain reaction analyses and probe arrays. One preferred diagnostic method for the detection of mRNA levels involves contacting the isolated mRNA with a nucleic acid molecule (probe) that can hybridise to the mRNA encoded by the gene being detected. The nucleic acid probe can be, for example, a full-length cDNA, or a portion thereof, such as an oligonucleotide of at least 7, 15, 30, 50, 100, 250 or 500 nucleotides in length and sufficient to specifically hybridise under stringent conditions to a mRNA encoding a marker of the present invention. Other suitable probes for use in the pronostic assays of the invention are described herein. Hybridisation of an mRNA with the probe indicates that the marker in question is being expressed. 
     In most preferred embodiments of step b) of the in vitro prediction method according to the invention, detection and/or quantification of the metastasis-specific biological markers is performed by using suitable DNA microarrays. In such a marker detection/quantification format, the mRNA is immobilised on a solid surface and contacted with a probe, for example by running the isolated mRNA on an agarose gel and transferring the mRNA from the gel to a membrane, such as nitrocellulose. In an alternative format, the probe(s) are immobilized on a solid surface and the mRNA is contacted with the probe(s), for example, in an Affymetrix gene chip array. A skilled artisan can readily adapt known mRNA detection methods for use in detecting the level of mRNA encoded by the markers of the present invention. Specific hybridization technology which may be practiced to generate the expression profiles employed in the subject methods includes the technology described in U.S. Pat. Nos. 5,143,854; 5,288,644; 5,324,633; 5,432,049; 5,470,710; 5,492,806; 5,503,980; 5,510,270; 5,525,464; 5,547,839; 5,580,732; 5,661,028; 5,800,992; the disclosures of which are herein incorporated by reference; as well as WO 95/21265; WO 96/31622; WO 97/10365; WO 97/27317; EP 373 203; and EP 785 280. In these methods, an array of “probe” nucleic acids that includes a probe for each of the phenotype determinative genes whose expression is being assayed is contacted with target nucleic acids as described above. Contact is carried out under hybridization conditions, e.g., stringent hybridization conditions as described above, and unbound nucleic acid is then removed. The resultant pattern of hybridized nucleic acid provides information regarding expression for each of the genes that have been probed, where the expression information is in terms of whether or not the gene is expressed and, typically, at what level, where the expression data, i.e., expression profile, may be both qualitative and quantitative. 
     An alternative method for determining the level of mRNA marker in a sample involves the process of nucleic acid amplification, e.g., by rtPCR (the experimental embodiment set forth in Mullis, 1987, U.S. Pat. No. 4,683,202), ligase chain reaction (Barany, 1991, Proc. Natl. Acad. Sci. USA, 88:189-193), self sustained sequence replication (Guatelli et al., 1990, Proc. Natl. Acad. Sci. USA 87:1874-1878), transcriptional amplification system (Kwoh et al., 1989, Proc. Natl. Acad. Sci. USA 86:1173-1177), Q-Beta Replicase (Lizardi et al., 1988, Bio/Technology 6:1197), rolling circle replication (Lizardi et al., U.S. Pat. No. 5,854,033) or any other nucleic acid amplification method, followed by the detection of the amplified molecules using techniques well known to those of skill in the art. These detection schemes are especially useful for the detection of nucleic acid molecules if such molecules are present in very low numbers. As used herein, amplification primers are defined as being a pair of nucleic acid molecules that can anneal to 5′ or 3′ regions of a gene (plus and minus strands, respectively, or vice-versa) and contain a short region in between. In general, amplification primers are from about 10 to 30 nucleotides in length and flank a region from about 50 to 200 nucleotides in length. Under appropriate conditions and with appropriate reagents, such primers permit the amplification of a nucleic acid molecule comprising the nucleotide sequence flanked by the primers. 
     For in situ methods, mRNA does not need to be isolated from the breast cancer prior to detection. In such methods, a cell or tissue sample is prepared/processed using known histological methods. The sample is then immobilised on a support, typically a glass slide, and then contacted with a probe that can hybridise to mRNA that encodes the marker. 
     As an alternative to making determinations based on the absolute expression level of the marker, determinations may be based on the normalised expression level of the marker. Expression levels are normalised by correcting the absolute expression level of a marker by comparing its expression to the expression of a gene that is not a marker, e.g., a housekeeping gene that is constitutively expressed. Suitable genes for normalisation include housekeeping genes such as the actin gene, ribosomal 18S gene, GAPDH gene and TATA-box-binding protein (TBP). This normalisation allows the comparison of the expression level of one or more tissue-specific biological marker of interest in one sample. 
     Alternatively, the expression level can be provided as a relative expression level. To determine a relative expression level of a marker, the level of expression of the marker is determined for 10 or more samples of normal versus cancer cell isolates, preferably 50 or more samples, prior to the determination of the expression level for the sample in question. The median expression level of each of the genes assayed in the larger number of samples is determined and this is used as a baseline expression level for the marker. The expression level of the marker determined for the test sample (absolute level of expression) is then divided by the mean expression value obtained for that marker. This provides a relative expression level. 
     As already mentioned previously in the present specification, the detection/quantification reagent for detecting and/or quantifying a biological marker protein when performing the metastasis prediction method of the invention may consist of an antibody that specifically bind to such a biological marker protein or a fragment thereof, preferably an antibody with a detectable label. Antibodies can be polyclonal, or more preferably, monoclonal. An intact antibody, or a fragment or derivative thereof (e.g., Fab or F(ab&#39;).sub.2) can be used. The term “labelled”, with regard to the probe or antibody, is intended to encompass direct labelling of the probe or antibody by coupling (i.e., physically linking) a detectable substance to the probe or antibody, as well as indirect labelling of the probe or antibody by reactivity with another reagent that is directly labelled. Examples of indirect labelling include detection of a primary antibody using a fluorescently labelled secondary antibody and end-labelling of a DNA probe with biotin such that it can be detected with fluorescently labelled streptavidin. 
     One skilled in the art will know many other suitable carriers for binding antibody or antigen, and will be able to adapt such support for use with the present invention. For example, protein isolated from breast cancer can be run on a polyacrylamide gel electrophoresis and immobilised onto a solid phase support such as nitrocellulose. The support can then be washed with suitable buffers followed by treatment with the detectably labeled antibody. The solid phase support can then be washed with the buffer a second time to remove unbound antibody. The amount of bound label on the solid support can then be detected by conventional means. 
     The most preferred methods for quantifying a biological marker for the purpose of carrying out the metastasis prediction method of the invention are described hereunder. 
     Quantifying Biological Markers by cDNA Microarrays 
     According to this embodiment, a microarray may be constructed based on the metastasis-specific markers that are disclosed throughout the present specification. Metastasis-specific detection reagents including these markers may be placed on the microarray. These cancer metastasis-specific detection reagents may be different than those used in PCR methods. However, they should be designed and used in conditions such that only nucleic acids having the metastasis-specific marker may hybridize and give a positive result. 
     Most existing microarrays, such as those provided by Affymetrix (California), may be used with the present invention. 
     One of skill in the art will appreciate that an enormous number of array designs are suitable. The high density array will typically include a number of probes that specifically hybridize to the sequences of interest. See WO 99/32660 for methods of producing probes for a given gene or genes. In a preferred embodiment, the array will include one or more control probes. 
     Nucleic Acid Probes Immobilized on the Microarray Devices 
     High density array chips include &lt;&lt;test probes&gt;&gt; that specifically hybridize with mRNAs or cDNAs consisting of the products of expression of the meatstasis-specific biological markers that are described herein. 
     Test probes may be oligonucleotides that range from about 5 to about 500 or about 5 to about 200 nucleotides, more preferably from about 10 to about 100 nucleotides and most preferably from about 15 to about 70 nucleotides in length. In other particularly preferred embodiments, the probes are about 20 or 25 nucleotides in length. In another preferred embodiment, test probes are double or single strand DNA sequences. DNA sequences may be isolated or cloned from natural sources or amplified from natural sources using natural nucleic acid as templates. These probes have sequences complementary to particular subsequences of the metastasis-specific markers whose expression they are designed to detect. 
     In addition to test probes that bind the target nucleic acid(s) of interest, the high density array can contain a number of control probes. The control probes fall into three categories referred to herein as normalization controls; expression level controls; and mismatch controls. Normalization controls are oligonucleotide or other nucleic acid probes that are complementary to labeled reference oligonucleotides or other nucleic acid sequences that are added to the nucleic acid sample. The signals obtained from the normalization controls after hybridization provide a control for variations in hybridization conditions, label intensity, “reading” efficiency and other factors that may cause the signal of a perfect hybridization to vary between arrays. In a preferred embodiment, signals (e.g. fluorescence intensity) read from all other probes in the array are divided by the signal (, fluorescence intensity) from the control probes thereby normalizing the measurements. Virtually any probe may serve as a normalization control. However, it is recognized that hybridization efficiency varies with base composition and probe length. Preferred normalization probes are selected to reflect the average length of the other probes present in the array; however, they can be selected to cover a range of lengths. The normalization control(s) can also be selected to reflect the (average) base composition of the other probes in the array, however in a preferred embodiment, only one or a few probes are used and they are selected such that they hybridize well (i.e., no secondary structure) and do not match any target-specific probes. Expression level controls are probes that hybridize specifically with constitutively expressed genes in the biological sample. Virtually any constitutively expressed gene provides a suitable target for expression level controls. Typical expression level control probes have sequences complementary to subsequences of constitutively expressed “housekeeping genes” including the .beta.-actin gene, the transferrin receptor gene, and the GAPDH gene. Mismatch controls may also be provided for the probes to the target genes, for expression level controls or for normalization controls. Mismatch controls are oligonucleotide probes or other nucleic acid probes identical to their corresponding test or control probes except for the presence of one or more mismatched bases. A mismatched base is a base selected so that it is not complementary to the corresponding base in the target sequence to which the probe would otherwise specifically hybridize. One or more mismatches are selected such that under appropriate hybridization conditions (e.g., stringent conditions) the test or control probe would be expected to hybridize with its target sequence, but the mismatch probe would not hybridize (or would hybridize to a significantly lesser extent). Preferred mismatch probes contain a central mismatch. Thus, for example, where a probe is a twenty-mer, a corresponding mismatch probe may have the identical sequence except for a single base mismatch (e.g., substituting a G, a C or a T for an A) at any of positions 6 through 14 (the central mismatch). Mismatch probes thus provide a control for non-specific binding or cross hybridization to a nucleic acid in the sample other than the target to which the probe is directed. Mismatch probes also indicate whether hybridization is specific or not. 
     Solid Supports for DNA Microarrays 
     Solid supports containing oligonucleotide probes for differentially expressed genes can be any solid or semisolid support material known to those skilled in the art. Suitable examples include, but are not limited to, membranes, filters, tissue culture dishes, polyvinyl chloride dishes, beads, test strips, silicon or glass based chips and the like. Suitable glass wafers and hybridization methods are widely available. Any solid surface to which oligonucleotides can be bound, either directly or indirectly, either covalently or non-covalently, can be used. In some embodiments, it may be desirable to attach some oligonucleotides covalently and others non-covalently to the same solid support. A preferred solid support is a high density array or DNA chip. These contain a particular oligonucleotide probe in a predetermined location on the array. Each predetermined location may contain more than one molecule of the probe, but each molecule within the predetermined location has an identical sequence. Such predetermined locations are termed features. There may be, for example, from 2, 10, 100, 1000 to 10,000, 100,000 or 400,000 of such features on a single solid support. The solid support or the area within which the probes are attached may be on the order of a square centimeter. Methods of forming high density arrays of oligonucleotides with a minimal number of synthetic steps are known. The oligonucleotide analogue array can be synthesized on a solid substrate by a variety of methods, including, but not limited to, light-directed chemical coupling, and mechanically directed coupling (see U.S. Pat. No. 5,143,854 to Pirrung et al.; U.S. Pat. No. 5,800,992 to Fodor et al.; U.S. Pat. No. 5,837,832 to Chee et al. 
     In brief, the light-directed combinatorial synthesis of oligonucleotide arrays on a glass surface proceeds using automated phosphoramidite chemistry and chip masking techniques. In one specific implementation, a glass surface is derivatized with a silane reagent containing a functional group, e.g., a hydroxyl or amine group blocked by a photolabile protecting group. Photolysis through a photolithographic mask is used selectively to expose functional groups which are then ready to react with incoming 5′ photoprotected nucleoside phosphoramidites. The phosphoramidites react only with those sites which are illuminated (and thus exposed by removal of the photolabile blocking group). Thus, the phosphoramidites only add to those areas selectively exposed from the preceding step. These steps are repeated until the desired array of sequences has been synthesized on the solid surface. Combinatorial synthesis of different oligonucleotide analogues at different locations on the array is determined by the pattern of illumination during synthesis and the order of addition of coupling reagents. 
     In addition to the foregoing, methods which can be used to generate an array of oligonucleotides on a single substrate are described in WO 93/09668 to Fodor et al. High density nucleic acid arrays can also be fabricated by depositing premade or natural nucleic acids in predetermined positions. Synthesized or natural nucleic acids are deposited on specific locations of a substrate by light directed targeting and oligonucleotide directed targeting. Another embodiment uses a dispenser that moves from region to region to deposit nucleic acids in specific spots. 
     Oligonucleotide probe arrays for expression monitoring can be made and used according to any techniques known in the art (see for example, Lockhart et al., Nat. Biotechnol. 14, 1675-1680 (1996); McGall et al., Proc. Nat. Acad. Sci. USA 93, 13555-13460 (1996). Such probe arrays may contain at least two or more oligonucleotides that are complementary to or hybridize to two or more of the genes described herein. Such arrays may also contain oligonucleotides that are complementary to or hybridize to at least 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 50, 70 or more of the genes described therein. 
     Gene Signature Differential Analysis. 
     Gene Signature Differential analysis is a method designed to detect nucleic acids, like mRNAs or cDNAs differentially expressed in different samples. 
     Hybridization 
     Nucleic acid hybridization simply involves contacting a probe and target nucleic acid under conditions where the probe and its complementary target can form stable hybrid duplexes through complementary base pairing (see WO 99/32660 to Lockhart). The nucleic acids that do not form hybrid duplexes are then washed away leaving the hybridized nucleic acids to be detected, typically through detection of an attached detectable label. It is generally recognized that nucleic acids are denatured by increasing the temperature or decreasing the salt concentration of the buffer containing the nucleic acids. Under low stringency conditions (e.g., low temperature and/or high salt) hybrid duplexes (e.g., DNA-DNA, RNA-RNA or RNA-DNA) will form even where the annealed sequences are not perfectly complementary. Thus, specificity of hybridization is reduced at lower stringency. Conversely, at higher stringency (e.g., higher temperature or lower salt) successful hybridization requires fewer mismatches. One of skill in the art will appreciate that hybridization conditions may be selected to provide any degree of stringency. In a preferred embodiment, hybridization is performed at low stringency, in this case in 6.times.SSPE-T at 37.degree. C. (0.005% Triton x-100) to ensure hybridization and then subsequent washes are performed at higher stringency (e.g., 1.times.SSPE-T at 37.degree. C.) to eliminate mismatched hybrid duplexes. Successive washes may be performed at increasingly higher stringency (e.g. down to as low as 0.25.times.SSPE-T at 37.degree. C. to 50.degree. C.) until a desired level of hybridization specificity is obtained. Stringency can also be increased by addition of agents such as formamide. Hybridization specificity may be evaluated by comparison of hybridization to the test probes with hybridization to the various controls that can be present (e.g., expression level controls, normalization controls, mismatch controls, etc.). 
     In general, there is a tradeoff between hybridization specificity (stringency) and signal intensity. Thus, in a preferred embodiment, the wash is performed at the highest stringency that produces consistent results and that provides a signal intensity greater than approximately 10% of the background intensity. The hybridized array may be washed at successively higher stringency solutions and read between each wash. Analysis of the data sets thus produced will reveal a wash stringency above which the hybridization pattern is not appreciably altered and which provides adequate signal for the particular oligonucleotide probes of interest. 
     Signal Detection 
     The hybridized nucleic acids are typically detected by detecting one or more labels attached to the sample nucleic acids. The labels may be incorporated by any of a number of means well known to those of skill in the art (see WO 99/32660 to Lockhart). Any suitable methods can be used to detect one or more of the markers described herein. For example, gas phase ion spectrometry can be used. This technique includes, e.g., laser desorption/ionization mass spectrometry. In some embodiments, the sample can be prepared prior to gas phase ion spectrometry, e.g., pre-fractionation, two-dimensional gel chromatography, high performance liquid chromatography, etc. to assist detection of markers. 
     Quantifying Biological Markers by Immunohistochemistry on Conventional Tissue Slides (Paraffin-Embedded or Frozen Specimens) 
     In certain embodiments, a biological marker, or a set of biological markers, may be quantified with any one of the immunohistochemistry methods known in the art. 
     Typically, for further analysis, one thin section of the tumour, is firstly incubated with labelled antibodies directed against one biological marker of interest. After washing, the labelled antibodies that are bound to said biological marker of interest are revealed by the appropriate technique, depending of the kind of label, e.g. radioactive, fluorescent or enzyme label. Multiple labelling can be performed simultaneously. 
     Quantifying Biological Markers by Nucleic Acid Amplification 
     In certain embodiments, a biological marker, or a set of biological markers, may be quantified with any one of the nucleic acid amplification methods known in the art. 
     The polymerase chain reaction (PCR) is a highly sensitive- and powerful method for such biological markers quantification 
     For performing any one of the nucleic acid amplification method that is appropriate for quantifying a biological marker when performing the metastasis prediction method of the invention, a pair of primers that specifically hybridise with the target mRNA or with the target cDNA is required. 
     A pair of primers that specifically hybridise with the target nucleic acid biological marker of interest may be designed by any one of the numerous methods known in the art. 
     In certain embodiments, for each of the biological markers of the invention, at least one pair of specific primers, as well as the corresponding detection nucleic acid probe, is already referenced and entirely described in the public “Quantitative PCR primer database”, notably at the following Internet address: http://lpgws.nci.nih.gov/cgi-bin/PrimerViewer. 
     In other embodiments, a specific pair of primers may be designed using the method disclosed in the U.S. Pat. No. 6,892,141 to Nakae et al., the entire disclosure of which is herein incorporated by reference. 
     Many specific adaptations of the PCR technique are known in the art for both qualitative and quantitative detection purposes. In particular, methods are known to utilise fluorescent dyes for detecting and quantifying amplified PCR products. In situ amplification and detection, also known as homogenous PCR, have also been previously described. See e.g. Higuchi et al., (Kinetics PCR Analysis: Real-time Monitoring of DNA Amplification Reactions, Bio/Technology, Vol 11, pp 1026-1030 (1993)), Ishiguro et al., (Homogeneous quantitative Assay of Hepatitis C Virus RNA by Polymerase Chain Reaction in the Presence of a Fluorescent Intercalater, Anal. Biochemistry 229, pp 20-213 (1995)), and Wittwer et al., (Continuous Fluorescence Monitoring of Rapid cycle DNA Amplification, Biotechniques, vol. 22, pp 130-138 (1997.)) 
     A number of other methods have also been developed to quantify nucleic acids (Southern, E. M., J. Mol. Biol., 98:503-517, 1975; Sharp, P. A., et al., Methods Enzymol. 65:750-768, 1980; Thomas, P. S., Proc. Nat. Acad. Sci., 77:5201-5205, 1980). More recently, PCR and RT-PCR methods have been developed which are capable of measuring the amount of a nucleic acid in a sample. One approach, for example, measures PCR product quantity in the log phase of the reaction before the formation of reaction products plateaus (Kellogg, D. E., et al., Anal. Biochem. 189:202-208 (1990); and Pang, S., et al., Nature 343:85-89 (1990)). A gene sequence contained in all samples at relatively constant quantity is typically utilised for sample amplification efficiency normalisation. This approach, however, suffers from several drawbacks. The method requires that each sample have equal input amounts of the nucleic acid and that the amplification efficiency between samples be identical until the time of analysis. Furthermore, it is difficult using the conventional methods of PCR quantitation such as gel electrophoresis or plate capture hybridisation to determine that all samples are in fact analysed during the log phase of the reaction as required by the method. 
     Another method called quantitative competitive (QC)-PCR, as the name implies, relies on the inclusion of an internal control competitor in each reaction (Becker-Andre, M., Meth. Mol. Cell Biol. 2:189-201 (1991); Piatak, M. J., et al., BioTechniques 14:70-81 (1993); and Piatak, M. J., et al., Science 259:1749-1754 (1993)). The efficiency of each reaction is normalised to the internal competitor. A known amount of internal competitor is typically added to each sample. The unknown target PCR product is compared with the known competitor PCR product to obtain relative quantitation. A difficulty with this general approach lies in developing an internal control that amplifies with the same efficiency of the target molecule. 
     For instance, the nucleic acid amplification method that is used may consist of Real-Time quantitative PCR analysis. 
     Real-time or quantitative PCR (QPCR) allows quantification of starting amounts of DNA, cDNA, or RNA templates. QPCR is based on the detection of a fluorescent reporter molecule that increases as PCR product accumulates with each cycle of amplification. Fluorescent reporter molecules include dyes that bind double-stranded DNA (i.e. SYBR Green I) or sequence-specific probes (i.e. Molecular Beacons or TaqMan® Probes). 
     Preferred nucleic acid amplification methods are quantitative PCR amplification methods, including multiplex quantitative PCR method such as the technique disclosed in the published US patent Application n o  US 2005/0089862, to Therianos et al., the entire disclosure of which is herein incorporated by reference. 
     Illustratively, for quantifying biological markers of the invention, tumor tissue samples are snap-frozen shortly after biopsy collection. Then, total RNA from a “tumour tissue sample” is isolated and quantified. Then, each sample of the extracted and quantified RNA is reverse-transcribed and the resulting cDNA is amplified by PCR, using a pair of specific primers for each biological marker that is quantified. Control pair of primers are simultaneously used as controls, such as pair of primers that specifically hybridise with TBP cDNA, 18S cDNA and GADPH cDNA, or any other well known “housekeeping” gene. 
     Illustrative embodiments of detection and quantification of the tissue-specific biological markers using nucleic acid amplification methods are disclosed in the examples herein. 
     The sequences of specific pairs of nucleic acid primers for detecting and/or quantifying various tissue-specific biological markers specified herein are expressly listed. 
     Further pairs of primers for detecting and/or quantifying the same tissue-specific biological markers are obtainable by the one skilled in the art, starting from the nucleic acid sequences of the said markers that are publicly available in the sequence databases. 
     Also, pairs of primers for the other tissue-specific markers disclosed herein are obtainable by the one skilled in the art, starting from the nucleic acid sequences of the said markers that are publicly available in the sequence databases. 
     Illustratively, specific pairs of primers that may be used for detecting and/or amplifying various tissue-specific biological markers are found below:
         (i) bone metastasis-specific markers: KTCD1 (SEQ ID No 1 and 2), BAIAP2L1 (SEQ ID No 3 and 4), PERP (SEQ ID No 5 and 6), CFD (SEQ ID No 7 and 8), CD4 (SEQ ID No 9 and 10), COL6A2 (SEQ ID No 11 and 12), FLI1 (SEQ ID No 13 and 14), PSTPIP1 (SEQ ID No 15 and 16), MGF10 (SEQ ID No 17 and 18), PTPN22 (SEQ ID No 19 and 20), FAM78A (SEQ ID No 21 and 22), NXF1 (SEQ ID No 23 and 24), MFNG (SEQ ID No 25 and 26) and CLEC4A (SEQ ID No 27 and 28);   (ii) lung metastasis-specific markers: KIND1 (SEQ ID No 29 and 30), ELAC1 (SEQ ID No 31 and 32), ANP32E (SEQ ID No 33 and 34), PAQR3 (SEQ ID No 35 and 36), ITGB8 (SEQ ID No 37 and 38), c1orf210 (SEQ ID No 39 and 40), SIKE (SEQ ID No 41 and 42), UGT8 (SEQ ID No 43 and 44), CALB2       

     (SEQ ID No 45 and 46), CHODL (SEQ ID No 47 and 48), c21orf91 (SEQ ID No 49 and 50), TFCP2L1 (SEQ ID No 51 and 52), ODF2L (SEQ ID No 53 and 54), HORMAD1 (SEQ ID No 55 and 56), PLEKHG4 (SEQ ID No 57 and 58) and DSC2 (SEQ ID No 59 and 60);
         (iii) liver metastasis-specific makers: GATA2 (SEQ ID No 61 and 62), SELT (SEQ ID No 63 and 64), WHSC1L1 (SEQ ID No 65 and 66), MYRIP (SEQ ID No 67 and 68), ZMAT1 (SEQ ID No 69 and 70), IL20RA (SEQ ID No 71 and 72), ZNF44 (SEQ ID No 73 and 74), LETM2 (SEQ ID No 75 and 76), AGXT2L1 (SEQ ID No 77 and 78), c5orf30 (SEQ ID No 79 and 80) and TBX3 (SEQ ID No 81 and 82).   (iv) brain metastasis-specific markers: PPWD1 (SEQ ID No 83 and 84), PDGFRA (SEQ ID No 85 and 86), MLL5 (SEQ ID No 87 and 88), RPS23 (SEQ ID No 89 and 90), ANTXR1 (SEQ ID No 91 and 92), ARRDC3 (SEQ ID No 93 and 94), METTL7A (SEQ ID No 95 and 96), NPHP3 (SEQ ID No 97 and 98), RSHL1 (SEQ ID No 99 and 100), CSPP1 (SEQ ID No 101 and 102), HOXB13       

     (SEQ ID No 103 and 104), TRA16 (SEQ ID No 105 and 106), DDX27 (SEQ ID No 107 and 108), PKP2 (SEQ ID No 109 and 110) and INHA (SEQ ID No 111 and 112). 
     A pair of primers that may be used for quantifying the TATA-box Binding Protein (TBP) as a control consists of the nucleic acids of SEQ ID No 113-114 disclosed herein. 
     The primers having the nucleic acid sequences SEQ ID No 1 to SEQ ID No 114 are also described in Table 3 herein. 
     Kits for Predicting Metastasis in Breast Cancer 
     The invention also relates to a kit for the in vitro prediction of the occurrence of metastasis in one or more tissue or organ in a patient (e.g. in a tumour tissue sample previously collected from a breast cancer patient). The kit comprises a plurality of reagents, each of which is capable of binding specifically with a biological marker nucleic acid or protein. 
     Suitable reagents for binding with a marker protein include antibodies, antibody derivatives, antibody fragments, and the like. 
     Suitable reagents for binding with a marker nucleic acid (e.g. a genomic DNA, an mRNA, a spliced mRNA, a cDNA, or the like) include complementary nucleic acids. For example, the nucleic acid reagents may include oligonucleotides (labelled or non-labelled) fixed to a substrate, labelled oligonucleotides not bound with a substrate, pairs of PCR primers, molecular beacon probes, and the like. 
     Another object of the present invention consists of a kit for the in vitro prediction of the occurrence of metastasis in a patient, which kit comprises means for detecting and/or quantifying one or more biological markers that are indicative of an occurrence of metastasis in one or more tissue or organ, wherein the said one or more biological markers are selected from the group consisting of:
         (i) one or more biological markers indicative of an occurrence of metastasis in the bone tissue that are selected from the group consisting of: CLEC4A, MFNG, NXF1, FAM78A, KCTD1, BAIAP2L1, PTPN22, MEGF10, PERP, PSTPIP1, FLI1, COL6A2, CD4, CFD, ZFHX1B, CD33, LST1, MMRN2, SH2D3C, RAMPS, FAM26B, ILK, TM6SF1, C10orf54, CLEC3B, IL2RG, HOM-TES-103, ZNF23, STK35, TNFAIP8L2, RAMP2, ENG, ACRBP, TBC1D10C, C11orf48, EBNA1BP2, HSPE1, GAS6, HCK, SLC2A5, RASA3, ZNF57, WASPIP, KCNK1, GPSM3, ADCY4, AIF1, NCKAP1, AMICA1, POP7, GMFG, PPM1M, CDGAP, GIMAP1, ARHGAP9, APOB48R, OCIAD2, FLRT2, P2RY8, RIPK4, PECAM1, URP2, BTK, APBB1IP, CD37, STARD8, GIMAP6, E2F6, WAS, HLA-DQB1, HVCN1, L0056902, ORC5L, MEF2C, PLCL2, PLAC9, RAC2, SYNE1, DPEP2, MYEF2, HSPD1, PSCD4, NXT1, LOC340061, ITGB3, AP1S2, SNRPG, CSF1, BIN2, ANKRD47, LIMS2, DARC, PTPN7, MSH6, GGTA1, LRRC33, GDPD5, CALC0001, FAM110C, BCL6B, LOC641700, ARHGDIB, DAAM2, TNFRSF14, TPSAB1, CSF2RA, RCSD1, F1121438, LOC133874, GSN, SLIT3, FYN, NCF4, PTPRC, EVI2B, SCRIB, C11orf31, LOC440731, TFAM, ARPC5L, PARVG, GRN, LMO2, CRSP8, EHBP1L1, HEATR2, NAALADL1, INPP5D, LTB, STRBP, FAM65A, ADARB1, TMEM140, DENND1C, PRPF19, CASP10SLC37A2, RHOJ, MPHOSPH10, PPIH, RASSF1, HDST, C16orf54, EPB41L4B, LRMP, LAPTM5, PRDM2, CYGB, LYCAT, ACP5, CMKLR1, UBE1L, MAN2C1, TNFSF12, C7orf24, Cxorf15, CUL1, SMAD7, ITGB7, APOL3, PGRMC1, PPA1, YES1, FBLN1, MRC2, PTK9L, LRP1, IGFBP5, WDR3, GTPBP4, SPI1, SELPLG, OSCAR, LYL1, POLR2H, YWHAQ, ISG20L2, LGI14, KIF5B, NGRN, TYROBP, C5orf4, COX7A2, S100A4, MATK, TMEM33, DOK3, LOC150166, CIRBP, NIN, C10orf72, FMNL1, FATS, CHKB/CPT1B, SNRPA1, GIMAP4, C20orf18, LTBP2, GABS, NQO1, MARCH2, MYO1F, CDS1, SRD5A1, C20orf160, SLAMF7, ACTL6A, ABP1, RAE1, MAF, SEMA3G, P2RY13, ZDHHC7, ERG, FHL1, CLEC10A, INTS5, MYO15B, CTSW, PILRA, HN1, SCARA5, PRAM1, EBP, SIGLEC9, LGP1, DGUOK, GGCX, RABL5, ZBTB16, TPSAB1, NOP5/NOP58, CCND2, CD200, EPPK1, DKFZp586C0721, CCT6A, RIPK3, ARHGAP25, GNAI2, USP4, FAHD2A, LOC399959, LOC133308, HKDC1, CD93, GTF3C4, ITGB2, ELOVL6, TGFB111, ASCC3L1, FES, KCNMB1, AACS, ATP6VOD2, TMEM97, NUDT15, ATP6V1B2, CCDC86, FLJ10154, SCARF2, PRELP, ACHE, GIMAP8, PDE4DIP, NKG7, C20orf59, RHOG, TRPV2, TCP1, TNRC8, TNS1, IBSP, MMP9, NRIP2, OLFML2B, OMD, WIF1, ZEB2, ARL8, COL12A1, EBF and EBF3;   (ii) one or more biological markers indicative of an occurrence of metastasis in the lung tissue that are selected from the group consisting of: DSC2, HORMAD1, PLEKHG4, ODF2L, C21orf91, TFCP2L1, TTMA, CHODL, CALB2, UGT8, LOC146795, C1orf210, SIKE, ITGB8, PAQR3, ANP32E, C20orf42/FERMT1, ELAC1, GYLTL1B, SPSB1, CHRM3, PTEN, PIGL, CHRM3, CDH3;   (iii) one or more biological markers indicative of an occurrence of metastasis in the liver tissue that are selected from the group consisting of: TBX3, SYT17, LOC90355, AGXT2L1, LETM2, LOC145820, ZNF44, IL20RA, ZMAT1, MYRIP, WHSC1L1, SELT, GATA2, ARPC2, CAB39L, SLCI6A3, DHFRL1, PRRT3, CYP3A5, RPS6KA5, KIAA1505, ATP5S, ZFYVE16, KIAA0701, PEBP1, DDHD2, WWP1, CCNL1, ROBO2, FAM111B, THRAP2, CRSP9, KARCA1, SLC16A3, ARID4A, TCEAL1, SCAMP1, KIAAO701, EIF5A, DDX46, PEX7, BCL2L11, YBX1, UBE21, REXO2, AXUD1, C10orf2, ZNF548, FBXL16, LOC439911, LOC283874, ZNF587, FLJ20366, KIAAO888, BAG4, CALU, KIAA1961, USP30, NR4A2, FOXA1, FBXO15, WNK4, CDIPT, NUDT16L1, SMAD5, STXBP4, TTC6, LOC113386, TSPYL1, CIP29, C8orf1, SYDE2, SLC12A8, SLC25A18, C7, STAU2, TSC22D2, GADD45G, PHF3, TNRC6C, TCEAL3, RRN3, C5orf24, AHCTF1, LOC92497; and   (iv) one or more biological markers indicative of an occurrence of metastasis in the brain tissue that are selected from the group consisting of: LOC644215, BAT1, GPR75, PPWD1, INHA, PDGFRA, MLL5, RPS23, ANTXR1, ARRDC3, PTK2, SQSTM1, METTL7A, NPHP3, PKP2, DDX31, FAM119A, LLGL2, DDX27, TRA16, HOXB13, GNAS, CSPP1, COL8A1, RSHL1, DCBLD2, UBXD8, SURF2, ZNF655, RAC3, AP4M1, HEG1, PCBP2, SLC30A7, ATAD3A/ATAD3B, CHI3L1, MUC6, HMG20B, BCL7A, GGN, ARHGEF3, PALLD, TOP1, PCTK1, C20orf4, ZBTB1, MSH6, SETD5, POSTN, MOCS3, GABPA, ZSWIM1, ZNHIT2, LOC653352, ELL, ARPC4, ZNF277, VAV2, HNRPH3, LHX1, FAM83A, DIP2B, RBM10, PMPCA, TYSND1, RAB4B, DLC1, KIAA2018, TES, TFDP2, C3orf10, ZBTB38, PSMD7, RECK, JMJD1C, F1120273, CENPB, PLAC2, C6orf111, ATP10D, RNF146, XRRA1, NPAS2, APBA2BP, WDR34, SLK, SBF2, SON, MORC3, C3orf63, WDR54, STX7, ZNF512, KLHL9, LOC284889, ETV4, RMND5B, ARMCX1, SLC29A4, TRIB3, LRRC23, DDIT3, THUMPD3, MICAL-L2, PA2G4, TSEN54, LAS1L, MEA1, S100PBP, TRAF2, EMILIN3, KIAA1712, PRPF6, CHD9, JMJD1B, ANKS1A, CAPN5, EPC2, WBSCR27, CYB561, LLGL1, EDD1.       

     The present invention also encompasses various alternative embodiments of the said prediction kit, wherein the said prediction kit comprises combination of marker detection and/or marker quantification means, for detecting and/or quantifying various combinations of the markers described in the present specification. 
     In certain embodiments of the invention, the said prediction kit consists of a kit for the in vitro prediction of the occurrence of lung metastasis in a patient who is affected with a breast cancer, wherein the said kit comprises means for detecting and/or quantifying one or more biological markers that are indicative of an occurrence of metastasis in the lung tissue, wherein the said one or more biological markers are selected from the group consisting of DSC2, TFCP2L1, UGT8, ITGB8, ANP32E and FERMT1. 
     In certain embodiments of the said prediction kit, it comprises means for detecting and/or quantifying 2, 3, 4, 5 or all of the following lung-specific markers: DSC2, TFCP2L1, UGT8, ITGB8, ANP32E and FERMT1. 
     In further embodiments, the said prediction kit comprises means for detecting and/or quantifying the whole combination of the six following markers: DSC2, TFCP2L1, UGT8, ITGB8, ANP32E and FERMT1. 
     In yet further embodiments, the said prediction kit comprises means for detecting and/or quantifying exclusively the whole combination of the six following markers: DSC2, TFCP2L1, UGT8, ITGB8, ANP32E and FERMT1, together with means for detecting and/or quantifying one or more reference markers, e.g. markers corresponding to ubiquitously expressed genes or proteins like actin. 
     Most preferably, a prediction kit according to the invention consists of a DNA microarray comprising probes hybridizing to the nucleic acid expression products (mRNAs or cDNAs) of the metastasis-specific biological markers described herein. 
     Another object of the present invention consists of a kit for monitoring the anti-metastasis effectiveness of a therapeutic treatment of a patient affected with a breast cancer with a pharmaceutical agent, which kit comprises means for quantifying one or more biological markers that are indicative of an occurrence of metastasis in one or more tissue or organ, wherein the said one or more biological markers are selected from the group consisting of:
         (i) one or more biological markers indicative of an occurrence of metastasis in the bone tissue that are selected from the group consisting of: CLEC4A, MFNG, NXF1, FAM78A, KCTD1, BAIAP2L1, PTPN22, MEGF10, PERP, PSTPIP1, FLI1, COL6A2, CD4, CFD, ZFHX1B, CD33, LST1, MMRN2, SH2D3C, RAMP3, FAM26B, ILK, TM6SF1, C10orf54, CLEC3B, IL2RG, HOM-TES-103, ZNF23, STK35, TNFAIP8L2, RAMP2, ENG, ACRBP, TBC1D10C, C11orf48, EBNA1BP2, HSPE1, GAS6, HCK, SLC2A5, RASA3, ZNF57, WASPIP, KCNK1, GPSM3, ADCY4, AIF1, NCKAP1, AMICA1, POP7, GMFG, PPM1M, CDGAP, GIMAP1, ARHGAP9, APOB48R, OCIAD2, FLRT2, P2RY8, RIPK4, PECAM1, URP2, BTK, APBB1IP, CD37, STARD8, GIMAP6, E2F6, WAS, HLA-DQB1, HVCN1, L0056902, ORC5L, MEF2C, PLCL2, PLAC9, RAC2, SYNE1, DPEP2, MYEF2, HSPD1, PSCD4, NXT1, LOC340061, ITGB3, AP1S2, SNRPG, CSF1, BIN2, ANKRD47, LIMS2, DARC, PTPN7, MSH6, GGTA1, LRRC33, GDPD5, CALC0001, FAM110C, BCL6B, LOC641700, ARHGDIB, DAAM2, TNFRSF14, TPSAB1, CSF2RA, RCSD1, F1121438, LOC133874, GSN, SLIT3, FYN, NCF4, PTPRC, EVI2B, SCRIB, C11orf31, LOC440731, TFAM, ARPC5L, PARVG, GRN, LMO2, CRSP8, EHBP1L1, HEATR2, NAALADL1, INPP5D, LTB, STRBP, FAM65A, ADARB1, TMEM140, DENND1C, PRPF19, CASP10, SLC37A2, RHOJ, MPHOSPH10, PPIH, RASSF1, HCST, C16orf54, EPB41L4B, LRMP, LAPTM5, PRDM2, CYGB, LYCAT, ACP5, CMKLR1, UBE1L, MAN2C1, TNFSF12, C7orf24, Cxorf15, CUL1, SMAD7, ITGB7, APOL3, PGRMC1, PPA1, YES1, FBLN1, MRC2, PTK9L, LRP1, IGFBP5, WDR3, GTPBP4, SPI1, SELPLG, OSCAR, LYL1, POLR2H, YWHAQ, ISG20L2, LGI14, KIF5B, NGRN, TYROBP, C5orf4, COX7A2, S100A4, MATK, TMEM33, DOK3, LOC150166, CIRBP, NIN, C10orf72, FMNL1, FATS, CHKB/CPT1B, SNRPA1, GIMAP4, C20orf18, LTBP2, GABS, NQO1, MARCH2, MYO1F, CDS1, SRD5A1, C20orf160, SLAMF7, ACTL6A, ABP1, RAE1, MAF, SEMA3G, P2RY13, ZDHHC7, ERG, FHL1, CLEC10A, INTS5, MYO5B, CTSW, PILRA, HN1, SCARA5, PRAM1, EBP, SIGLEC9, LGP1, DGUOK, GGCX, RABL5, ZBTB16, TPSAB1, NOP5/NOP58, CCND2, CD200, EPPK1, DKFZp586CO721, CCT6A, RIPK3, ARHGAP25, GNAI2, USP4, FAHD2A, LOC399959, LOC133308, HKDC1, CD93, GTF3C4, ITGB2, ELOVL6, TGFB111, ASCC3L1, FES, KCNMB1, AACS, ATP6VOD2, TMEM97, NUDT15, ATP6V1B2, CCDC86, FLJ10154, SCARF2, PRELP, ACHE, GIMAP8, PDE4DIP, NKG7, C20orf59, RHOG, TRPV2, TCP1, TNRC8, TNS1, IBSP, MMP9, NRIP2, OLFML2B, OMD, WIF1, ZEB2, ARL8, COL12A1, EBF and EBF3,   (ii) one or more biological markers indicative of an occurrence of metastasis in the lung tissue that are selected from the group consisting of: DSC2, HORMAD1, PLEKHG4, ODF2L, C21orf91, TFCP2L1, TTMA, CHODL, CALB2, UGT8, LOC146795, C1orf210, SIKE, ITGB8, PAQR3, ANP32E, C20orf42, ELAC1, GYLTL1B, SPSB1, CHRM3, PTEN, PIGL, CHRM3, CDH3;   (iii) one or more biological markers indicative of an occurrence of metastasis in the liver tissue that are selected from the group consisting of: TBX3, SYT17, LOC90355, AGXT2L1, LETM2, LOC145820, ZNF44, IL20RA, ZMAT1, MYRIP, WHSC1 L1, SELT, GATA2, ARPC2, CAB39L, SLCI6A3, DHFRL1, PRRT3, CYP3A5, RPS6KA5, KIAA1505, ATP5S, ZFYVE16, KIAA0701, PEBP1, DDHD2, WWP1, CCNL1, ROBO2, FAM111B, THRAP2, CRSP9, KARCA1, SLC16A3, ARID4A, TCEAL1, SCAMP1, KIAAO701, EIF5A, DDX46, PEX7, BCL2L11, YBX1, UBE21, REXO2, AXUD1, C10orf2, ZNF548, FBXL16, LOC439911, LOC283874, ZNF587, FLJ20366, KIAAO888, BAG4, CALU, KIAA1961, USP30, NR4A2, FOXA1, FBXO15, WNK4, CDIPT, NUDT16L1, SMAD5, STXBP4, TTC6, LOC113386, TSPYL1, CIP29, C8orf1, SYDE2, SLC12A8, SLC25A18, C7, STAU2, TSC22D2, GADD45G, PHF3, TNRC6C, TCEAL3, RRN3, C5orf24, AHCTF1, LOC92497; and   (iv) one or more biological markers indicative of an occurrence of metastasis in the brain tissue that are selected from the group consisting of: LOC644215, BAT1, GPR75, PPWD1, INHA, PDGFRA, MLL5, RPS23, ANTXR1, ARRDC3, PTK2, SQSTM1, METTL7A, NPHP3, PKP2, DDX31, FAM119A, LLGL2, DDX27, TRA16, HOXB13, GNAS, CSPP1, COL8A1, RSHL1, DCBLD2, UBXD8, SURF2, ZNF655, RAC3, AP4M1, HEG1, PCBP2, SLC30A7, ATAD3A/ATAD3B, CHI3L1, MUC6, HMG20B, BCL7A, GGN, ARHGEF3, PALLD, TOP1, PCTK1, C20orf4, ZBTB1, MSH6, SETD5, POSTN, MOCS3, GABPA, ZSWIM1, ZNHIT2, LOC653352, ELL, ARPC4, ZNF277, VAV2, HNRPH3, LHX1, FAM83A, DIP2B, RBM10, PMPCA, TYSND1, RAB4B, DLC1, KIAA2018, TES, TFDP2, C3orf10, ZBTB38, PSMD7, RECK, JMJD1C, FLJ20273, CENPB, PLAC2, C6orf111, ATP10D, RNF146, XRRA1, NPAS2, APBA2BP, WDR34, SLK, SBF2, SON, MORC3, C3orf63, WDR54, STX7, ZNF512, KLHL9, LOC284889, ETV4, RMND5B, ARMCX1, SLC29A4, TRIB3, LRRC23, DDIT3, THUMPD3, MICAL-L2, PA2G4, TSEN54, LAS1L, MEA1, S100PBP, TRAF2, EMILIN3, KIAA1712, PRPF6, CHD9, JMJD1B, ANKS1A, CAPN5, EPC2, WBSCR27, CYB561, LLGL1, EDD1.       

     The present invention also encompasses various alternative embodiments of the said monitoring kit, wherein the said monitoring kit comprises combination of marker detection and/or marker quantification means, for detecting and/or quantifying various combinations of the markers described in the present specification. 
     In certain embodiments of the invention, the said monitoring kit consists of a kit for the in vitro prediction of the occurrence of lung metastasis in a patient who is affected with a breast cancer, wherein the said kit comprises means for detecting and/or quantifying one or more biological markers that are indicative of an occurrence of metastasis in the lung tissue, wherein the said one or more biological markers are selected from the group consisting of DSC2, TFCP2L1, UGT8, ITGB8, ANP32E and FERMT1. 
     In certain embodiments of the said monitoring kit, it comprises means for detecting and/or quantifying 2, 3, 4, 5 or all of the following lung-specific markers: DSC2, TFCP2L1, UGT8, ITGB8, ANP32E and FERMT1. 
     In further embodiments, the said monitoring kit comprises means for detecting and/or quantifying the whole combination of the six following markers: DSC2, TFCP2L1, UGT8, ITGB8, ANP32E and FERMT1. 
     In yet further embodiments, the said monitoring kit comprises means for detecting and/or quantifying exclusively the whole combination of the six following markers: DSC2, TFCP2L1, UGT8, ITGB8, ANP32E and FERMT1, together with means for detecting and/or quantifying one or more reference markers, e.g. markers corresponding to ubiquitously expressed genes or proteins like actin. 
     The prediction kit and the monitoring kit of the invention may optionally comprise additional components useful for performing the methods of the invention. By way of example, the kits may comprise fluids (e.g. SSC buffer) suitable for annealing complementary nucleic acids or for binding an antibody with a protein with which it specifically binds, one or more sample compartments, an instructional material which describes performance of the prediction method or of the monitoring method of the invention, and the like. 
     Kits Comprising Antibodies 
     In certain embodiments, a kit according to the invention comprises one or a combination or a set of antibodies, each kind of antibodies being directed specifically against one biological marker of the invention. 
     In one embodiment, said kit comprises a combination or a set of antibodies comprising at least two kind of antibodies, each kind of antibodies being selected from the group consisting of antibodies directed against one of the biological markers disclosed herein. 
     An antibody kit according to the invention may comprise 2 to 20 kinds of antibodies, each kind of antibodies being directed specifically against one biological marker of the invention. For instance, an antibody kit according to the invention may comprise 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 kinds of antibodies, each kind of antibodies being directed specifically against one biological marker as defined herein. 
     Various antibodies directed against biological markers according to the invention encompass antibodies directed against biological markers selected from the group consisting of those metastasis-specific markers that are listed in Table 4. Specific embodiments of these antibodies are listed in Table 4 herein. 
     Specific embodiments of a prediction kit according to the invention which contains detection/quantification means consisting of antibodies include the fluorescent microsphere-bound antibody suspension array technology, e.g. the kit technology that is marketed under the trademark Bio-Plex® by the Bio-Rad Company. 
     Concurrent with the increasing interest in magnetic microspheres for biological assays is the development of assays conducted on fluorescent microspheres. The use of fluorescent labels or fluorescent material coupled to a surface of the microspheres or incorporated into the microspheres allows preparation of numerous sets of microspheres that are distinguishable based on different dye emission spectra and/or signal intensity. In a biological assay, the fluorescence and light scattering of these microspheres can be measured by a flow cytometer or an imaging system, and the measurement results can be used to determine the size and fluorescence of the microspheres as well as the fluorescence associated with the assay system being studied (e.g., a fluorescently labeled antibody in a “capture sandwich” assay), as described in U.S. Pat. No. 5,948,627 to Lee et al., which is incorporated by reference as if fully set forth herein. By varying the concentrations of multiple dyes incorporated in the microspheres, hundreds, or even thousands, of distinguishable microsphere sets can be produced. In an assay, each microsphere set can be associated with a different target thereby allowing numerous tests to be conducted for a single sample in a single container as described in U.S. Pat. No. 5,981,180 to Chandler et al., which is incorporated by reference as if fully set forth herein. 
     Fluorescently distinguishable microspheres may be improved by rendering these microspheres magnetically responsive. Examples of methods for forming fluorescent magnetic microspheres are described in U.S. Pat. No. 5,283,079 to Wang et al., which is incorporated by reference as if fully set forth herein. The methods described by Wang et al. include coating a fluorescent core microsphere with magnetite and additional polymer or mixing a core microsphere with magnetite, dye, and polymerizable monomers and initiating polymerization to produce a coated microsphere. These methods are relatively simple approaches to the synthesis of fluorescent magnetic microspheres. 
     Additionally, for creating a large numbers of precisely dyed microspheres used in relatively large multiplex assays, those as described in U.S. Pat. No. 5,981,180 to Chandler et al. may be used. 
     Fluorescent magnetic microspheres are also described in U.S. Pat. No. 6,268,222 to Chandler et al., which is incorporated by reference as if fully set forth herein. In this method, nanospheres are coupled to a polymeric core microsphere, and the fluorescent and magnetic materials are associated with either the core microsphere or the nanospheres. This method produces microspheres with desirable characteristics. 
     A further embodiment of fluorescent magnetic microspheres is a magnetically responsive microspheres that can be dyed using established techniques, such as those described in U.S. Pat. No. 6,514,295 to Chandler et al. In general, this method uses solvents that swell the microsphere thereby allowing migration of the fluorescent material into the microsphere. These dyeing solvents include one or more organic solvents. 
     Also, magnetic microspheres are described in U.S. Pat. No. 5,091,206 to Wang et al., U.S. Pat. No. 5,648,124 to Sutor, and U.S. Pat. No. 6,013,531 to Wang et al., which are incorporated by reference as if fully set forth herein. 
     In certain other embodiments, a kit according to the invention comprises one or a combination or a set of pair of ligands or specfic soluble molecules binding with one or more of the biological marker(s), of the invention. 
     Kits Comprising Nucleic Acid Primers 
     In certain other embodiments, a kit according to the invention comprises one or a combination or a set of pair of primers, each kind of pair of primers hybridising specifically with one biological marker of the invention. 
     In one embodiment, said kit comprises a combination or a set of pair of primers comprising at least two kind of pair of primers, each kind of pair of primers being selected from the group consisting of pair of primers hybridising with one of the biological markers disclosed in the present specification, including the pairs of primers of SEQ ID No 1-112 that are detailed earlier in the specification. 
     A primer kit according to the invention may comprise 2 to 20 kinds of pair or primers, each kind of pair of primers hybridising specifically with one biological marker of the invention. For instance, a primer kit according to the invention may comprise 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 kinds of pairs of primers, each kind of pair of primers hybridising specifically against one biological marker as defined herein. 
     Notably, at least one pair of specific primers, as well as the corresponding detection nucleic acid probe, that hybridise specifically with one biological marker of interest, is already referenced and entirely described in the public “Quantitative PCR primer database”, notably at the following Internet address: http://lpgws.nci.nih.gov/cgi-bin/PrimerViewer. 
     Illustratively, a prediction kit or a monitoring kit according to the invention may comprise one or more specific pairs of primers for detecting and/or amplifying various tissue-specific biological markers, among the primers specified below:
         (i) bone metastasis-specific markers: KTCD1 (SEQ ID No 1 and 2), BAIAP2L1 (SEQ ID No 3 and 4), PERP (SEQ ID No 5 and 6), CFD (SEQ ID No 7 and 8), CD4 (SEQ ID No 9 and 10), COL6A2 (SEQ ID No 11 and 12), FLI1 (SEQ ID No 13 and 14), PSTPIP1 (SEQ ID No 15 and 16), MGF10 (SEQ ID No 17 and 18), PTPN22 (SEQ ID No 19 and 20), FAM78A (SEQ ID No 21 and 22), NXF1 (SEQ ID No 23 and 24), MFNG (SEQ ID No 25 and 26) and CLEC4A (SEQ ID No 27 and 28);   (ii) lung metastasis-specific markers: KIND1 (SEQ ID No 29 and 30), ELAC1 (SEQ ID No 31 and 32), ANP32E (SEQ ID No 33 and 34), PAQR3 (SEQ ID No 35 and 36), ITGB8 (SEQ ID No 37 and 38), c1orf210 (SEQ ID No 39 and 40), SIKE (SEQ ID No 41 and 42), UGT8 (SEQ ID No 43 and 44), CALB2 (SEQ ID No 45 and 46), CHODL (SEQ ID No 47 and 48), c21orf91 (SEQ ID No 49 and 50), TFCP2L1 (SEQ ID No 51 and 52), ODF2L (SEQ ID No 53 and 54), HORMAD1 (SEQ ID No 55 and 56), PLEKHG4 (SEQ ID No 57 and 58) and DSC2 (SEQ ID No 59 and 60);   (iii) liver metastasis-specific makers: GATA2 (SEQ ID No 61 and 62), SELT (SEQ ID No 63 and 64), WHSC1L1 (SEQ ID No 65 and 66), MYRIP (SEQ ID No 67 and 68), ZMAT1 (SEQ ID No 69 and 70), IL20RA (SEQ ID No 71 and 72), ZNF44 (SEQ ID No 73 and 74), LETM2 (SEQ ID No 75 and 76), AGXT2L1 (SEQ ID No 77 and 78), c5orf30 (SEQ ID No 79 and 80) and TBX3 (SEQ ID No 81 and 82).   (iv) brain metastasis-specific markers: PPWD1 (SEQ ID No 83 and 84), PDGFRA (SEQ ID No 85 and 86), MLL5 (SEQ ID No 87 and 88), RPS23 (SEQ ID No 89 and 90), ANTXR1 (SEQ ID No 91 and 92), ARRDC3 (SEQ ID No 93 and 94), METTL7A (SEQ ID No 95 and 96), NPHP3 (SEQ ID No 97 and 98), RSHL1 (SEQ ID No 99 and 100), CSPP1 (SEQ ID No 101 and 102), HOXB13 (SEQ ID No 103 and 104), TRA16 (SEQ ID No 105 and 106), DDX27 (SEQ ID No 107 and 108), PKP2 (SEQ ID No 109 and 110) and INHA (SEQ ID No 111 and 112).       

     These kits may also comprise one or more pairs of primers for detecting and/or quantifying a control marker. Illustratively, these kits may comprise a pair of primer for detecting and/or quantifying the TATA-box Binding Protein (TBP), such as the nucleic acids of SEQ ID No 113-114 disclosed herein. 
     Monitoring Anti-Cancer Treatments 
     Monitoring the influence of agents (e.g., drug compounds) on the level of expression of one or more tissue-specific biological markers of the invention can be applied for monitoring the metastatic potency of the treated breast cancer of the patient with time. For example, the effectiveness of an agent to affect biological marker expression can be monitored during treatments of subjects receiving anti-cancer, and especially anti-metastasis, treatments. 
     In a preferred embodiment, the present invention provides a method for monitoring the effectiveness of treatment of a subject with an agent (e.g., an agonist, antagonist, peptidomimetic, protein, peptide, nucleic acid, small molecule, or other drug candidate) comprising the steps of (i) obtaining a pre-administration sample from a subject prior to administration of the agent; (ii) detecting the level of expression of one or more selected biological markers of the invention in the pre-administration sample; (iii) obtaining one or more post-administration samples from the subject; (iv) detecting the level of expression of the biological marker(s) in the post-administration samples; (v) comparing the level of expression of the biological marker(s) in the pre-administration sample with the level of expression of the marker(s) in the post-administration sample or samples; and (vi) altering the administration of the agent to the subject accordingly. For example, decreased expression of the biological marker gene(s) during the course of treatment may indicate ineffective dosage and the desirability of increasing the dosage. Conversely, increased expression of the biological marker gene(s) may indicate efficacious treatment and no need to change dosage. 
     Because repeated collection of biological samples from the breast cancer-bearing patient are needed for performing the monitoring method described above, then preferred biological samples consist of blood samples susceptible to contain (i) cells originating from the patient&#39;s breast cancer tissue, or (ii) metastasis-specific marker expression products synthesized by cells originating from the patients breast cancer tissue, including nucleic acids and proteins. As used herein, the said “breast cancer patient&#39;s tissue includes the primary tumor tissue as well as a organ-specific or tissue-specific metastasis tissue. 
     As already mentioned previously in the present specification, performing the metastasis prediction method of the invention may indicate, with more precision than the prior art methods, those patients at high-risk of tumor recurrence who may benefit from adjuvant therapy, including immunotherapy. 
     For example, if, at the end of the metastasis prediction method of the invention, a good prognosis of no metastasis is determined, then the subsequent anti-cancer treatment will not comprise any adjuvant chemotherapy. 
     However, if, at the end of the metastasis prediction method of the invention, a bad prognosis with is determined, then the patient is administered with the appropriate composition of adjuvant chemotherapy. 
     Accordingly, the present invention also relates to a method for adapting a cancer treatment in a breast cancer patient, wherein said method comprises the steps of:
         a) performing, on at least one tumor tissue sample collected from said patient, the metastasis prediction method that is disclosed herein;   b) adapting the cancer treatment of the said cancer patient by administering to the said patient an adjuvant chemotherapy or an anti-metastasis therapy if a bad cancer prognosis with metastasis in one or more tissue or organ, including bone, lung, liver and brain, is determined at the end of step a).       

     Another object of the invention consists of a kit for monitoring the effectiveness of treatment (adjuvant or neo-adjuvant) of a subject with an agent, which kit comprises means for quantifying at least one biological marker of the invention that is indicative of the probability of occurrence of metastasis in a breast cancer patient. 
     Methods for Selecting Biological Markers Indicative of Metastasis 
     This invention also pertains to methods for selecting one or more biological markers that are indicative of the probability of occurrence of metastasis in one or more tissue or organ in a breast cancer-bearing patient. 
     The said tissue-specific marker selection method according to the invention preferably comprises the steps of:
         a) providing means for detecting and/or quantifying one or more biological markers in a tissue sample;   b) providing a plurality of collections of metastasis tissue samples originating from breast cancer patients wherein each of the said collection consists of a plurality of tissue samples originating from metastasis originating from a unique tissue type of metastatic breast cancer patients;   c) detecting and/or quantifying each of the one or more biological markers, separately in every tissue sample contained in each collection of tissue samples;   d) selecting, in the group of biological markers that are detected and/or quantified at step c), those markers that are expressed exclusively in only one collection of tissue samples that is comprised in the plurality of collections of tissue samples provided at step b), whereby a set of markers is selected for each collection of tissue samples, the said set of markers comprising markers, the expression of which is indicative of the probability of occurrence of metastasis in a specific tissue of a breast cancer patient.       

     For the purpose of performing the marker selection method above exclusively, the term “biological marker” is used in its conventionally acknowledged meaning by the one skilled in the art, i.e. herein a product of expression of any human gene, including nucleic acids and proteins. 
     Illustrative embodiments of the selection method above are fully described in the examples herein. 
     For performing step a) of the selection method above, the marker detection and/or quantification means encompass means for detecting or quantifying marker proteins, such as antibodies, or marker gene-specific nucleic acids, such as oligonucleotide primers or probes. Illustratively, DNA or antibodies microarrays may be used at step a) of the selection method above. 
     Means for specifically detecting and/or quantifying any one of the known biological marker, e.g. any known protein or any gene-specific nucleic acid, may be provided at step a) of the selection method. 
     Each collection of tissue samples that is provided at step b) of the selection method above comprises a number of metastasis tissue samples originating from a unique metastatic tissue (e.g. bone, lung, liver, brain and skin) that are collected from the same number of breast cancer-bearing individuals. Preferably, each collection of metastasis tissue samples comprises samples originating from at least 10 distinct breast cancer individuals, and most preferably at least 20, 25 or 30 distinct breast cancer individuals. The statistical relevance of the tissue-specific markers that are finally selected at the end of the selection method generally increases with the number of distinct breast cancer individuals tested, and thus with the number of metastasis tissue samples comprised in each collection that is provided at step b). 
     At step c), detection and/or quantification of the biological markers on the tissue samples provided at step b), using the detection and/or quantification means provided at step a), may be performed according to any one of the detection and/or quantification methods that are described elsewhere in the present specification. 
     At step d), each marker detected at step c) in a first specific collection of tissue samples (e.g. bone metastasis tissue) is compared to the detection and/or quantification results found for the same marker in all of the other collections of tissue samples (e.g. lung, liver and brain). Then, only those markers that are differentially expressed (i.e. (i) expressed, (ii) not expressed, (iii) over-expressed and (iv) under-expressed) in the said first collection of tissue samples, as compared to the other collections of tissue samples are positively selected as markers indicative of a probability of occurrence of breast cancer metastasis in the said specific tissue (e.g. bone metastasis tissue). At step d), the selection of statistically relevant metastasis tissue-specific markers, by comparing marker expression in one breast cancer metastatic tissue with the expression of the said marker in the group of all other distinct breast metastatic breast cancer tissue(s), is termed a “One Versus All” (“OVA”) pairwise comparison, as it is fully described in the examples herein. 
     The statistical relevance of each marker tested, at step d), may be performed by calculating the p value for the said marker, for example using a univariate t-test, as disclosed in the examples herein. Generally, a marker is selected at step d) of the selection method above, when its p value is lower than 10 −3 . 
     The statistical relevance of the marker selection, at step d) of the method, may be further increased by performing a multivariate permutation test, to provide 90% confidence that a false marker selection rate is less than 10%, as disclosed in the examples herein. 
     In view of further improving the relevancy of the marker selection, at step d), further selection filters may be included, such as removing every marker consisting of a tissue-specific gene, i.e. every marker that is selectively differentially expressed in a first specific normal non-cancerous tissue (e.g. bone), as compared to the other normal non-cancerous tissues (e.g. lung, liver, brain, etc.). 
     For further increasing the statistical relevance of the markers initially selected, at step d) of the selection method above, those markers that were initially selected as described above may be submitted to a further cycle of selection, for example by assaying the initially selected markers on further collections of breast cancer metastasis tissue samples. This further cycle of selection may consist of, for example, performing a further expression analysis of the initially selected markers, for example by technique of quantitative RT-PCR expression analysis, as shown in the examples herein. DNA microarrays may also be used. 
     According to such a quantitative RT-PCR expression analysis, the quantification measure of expression of each initially selected marker is normalised against a control value, e.g. the quantification measure of expression of a control gene such as TBP. The results may be expressed as N-fold difference of each marker relative to the value in normal breast tissues. Statistical relevance of each initially selected marker is then confirmed, for example at confidence levels of more than 95% (P of less than 0.05) using the Mann-Whitney U Test (SEM), as described in the examples herein. 
     The present invention is further illustrated by, without in any way being limited to, the examples below. 
     EXAMPLES 
     Examples 1 and 2 
     A. Materials and Methods of the Examples 1 and 2 
     A.1. Tissue Samples 
     A total of 33 metastases from human breast cancer were used for microarray and quantitative RT-PCR analyses. These samples were snap-frozen in liquid nitrogen and stored at ±196° C. Seven bone metastases (osteolytic type) and 6 normal bone samples were obtained from University of L&#39;Aquila (L&#39;Aquila, Italy), 4 brain metastases and 4 normal brain samples from IDIBELL (Barcelona, Spain). All other metastatic samples (8 lung, 8 liver and 6 skin metastases) and the 35 breast primary tumors samples were obtained from Centre René Huguenin (Saint-Cloud, France). All these primary tumor samples were resected from female patients who did not receive chemotherapy. Normal breast, lung, brain and liver RNA samples were purchased from Clontech, Biochain and Invitrogen. Normal tissue RNA pools were prepared with at least 5 samples each. Publicly available microarray data of a cohort of breast primary tumors with clinical follow up (with known site of relapse: bone, lung and other) were downloaded as on the NCBI website (GSE2603 record). 
     Additional breast cancer metastatic paraffin-embedded samples were obtained from the Department of Pathology (Pr. J. Boniver) at the University of Liège, Belgium (12 bone, 6 liver, 4 lung), from IDIBELL, Spain (6 brain), from the Anatomopathology Department of the Centre René Huguenin, France (2 lung and 1 liver) and used for the immunohistochemical analysis. 
     A.2. RNA Extraction 
     Total RNA was isolated from human samples using TRIzoL® Reagent from Gibco, as described by the manufacturer. RNA was quantified by absorbance at 260 nm (Nanodrop). Quality of the RNA samples was assessed by agarose gel electrophoresis and the integrity of 18S and 28S ribosomal RNA bands. Total RNA used for microarray analysis was further purified using RNeasy® spin columns (Qiagen) according to the manufacturers&#39; protocols. 
     A.3. Probe Preparation and Microarray Hybridization 
     Sample labeling, hybridization, and staining were carried out according to the Eukaryotic Target Preparation protocol in the Affymetrix® Technical Manual (701021 Rev. 5) for GeneChip® Expression analysis (Affymetrix). In summary, 500 ng-10 μg of purified total RNA was used to generate double-stranded cDNA using a GeneChip Expression 3′-Amplification One-Cycle cDNA synthesis Kit and a T7-oligo(dT) primer (Affymetrix). The resulting cDNA was purified using the GeneChip Sample Cleanup Module according to the manufacturers&#39; protocol (Affymetrix). The purified cDNA was amplified using GeneChip Expression 3′-Amplification Reagents For IVT Labelling (Affymetrix) to produce 20-70 μg of biotin labeled cRNA (complement RNA). 13 μg of labeled cRNA (per array) was fragmented at 94° C. for 35 min. The fragmented cRNA was hybridized to the Human Genome U133 Plus 2.0 Array for 16 h at 45° C. 
     The hybridized arrays were washed and stained using Streptavidin-Phycoerythrin (Molecular Probes) and amplified with biotinylated anti-streptavidin (Vector Laboratories) using a GeneChip Fluidics Station 450 (Affymetrix). The arrays were scanned in an Affymetrix GeneChip scanner 3000 at 570 nm. The 5′/3′ GAPDH ratios averaged 3.5 and the average background, noise average, % Present calls and average signal of the Present calls were comparable for all the arrays utilized in this experiment. U133 Plus 2.0 expression arrays contain 56000 probe sets corresponding to 47000 transcripts. 
     A.4. Microarray Statistical Analysis 
     Expression profiles were analyzed with BRB Array tools, version 3.3beta3 (Biometric Research Branch, Division of Cancer Treatment and Diagnosis Molecular Statistics and Bioinformatics Section, National Cancer Institute, Bethesda, Md., USA). Microarray data were collated as CEL files, calculation of Affymetrix probe set summaries and quantile normalization were done using RMA function of Bioconductor. We developed 4 raw site-specific metastatic signatures: bone, brain, liver and lung metastases. We used 6 bone, 4 brain, 6 liver, 5 lung and 2 skin metastases. We divided the multiclass problem into a series of 4 “One Versus All” (OVA) pairwise comparisons. For example, the raw bone metastasis signature was defined as follow: we selected probes differentially expressed between “Bone metastases” vs “All other metastases”, i.e. “Bone metastases” vs “Lung+Liver+Brain+Skin metastases”. 
     We identified genes that were differentially expressed among the two classes using a univariate t-test. Genes were considered statistically significant if their p value was less than 0.0001. A stringent significance threshold was used to limit the number of false positive findings. 
     We defined several selection filters. First, we identified potential host-tissue genes that could originate from contamination. Genes are considered as putative host-tissue genes if they are 1.5-fold more expressed in the corresponding normal tissue pool (e.g. bone) than in each of the other 3 normal tissue pools (i.e. liver, brain and lung). Second, upregulated genes with a geometric mean of intensities below 25 in the corresponding class (e.g., bone metastases) are removed. Downregulated genes with a geometric mean of intensities below 25 in the “other metastases” class (e.g. liver, brain, lung and skin metastases) are removed. Finally, probes were aligned against human genome (using Blast software from NCBI website). They were not conserved when they do not recognize transcripts. Metastatic signatures contain remaining most differentially expressed genes (sorted by absolute t-value) and were tested by quantitative RT-PCR. 
     A.5. Quantitative RT-PCR Expression Analysis 
     cDNA of human samples used for real-time RT-PCR analysis were synthesized as previously described (Bieche et al., 2001). All of the PCR reactions were performed using a ABI Prism 7700 Sequence Detection System (Perkin-Elmer Applied Biosystems) and the SYBR Green PCR Core Reagents kit (Perkin-Elmer Applied Biosystems). 10 μl of diluted sample cDNA (produced from 2 □g of total RNA) was added to 15 μl of the PCR master-mix. The thermal cycling conditions were composed of an initial denaturation step at 95° C. for 10 min, and 50 cycles at 95° C. for 15 s and 65° C. for 1 min. 
     Human RNAs from primary tumors and relapses were analyzed for expression of 56 genes selected among the organ-specific metastasis associated genes by using quantitative real-time reverse transcription-PCR (RT-PCR) assay, as previously described (Bieche et al., 2001). Expression of these genes were measured in 29 metastatic samples from human breast cancer including 19 already tested by microarray and10 new samples (1 bone, 3 lung, 2 liver, and 4 skin relapses). TATA-box-binding protein (TBP) transcripts were used as an endogenous RNA control, and each sample was normalized on the basis of its TBP content. Results, expressed as N-fold differences for each X gene expression relative to the TBP gene (termed “N X ”), were obtained with the formula N X =2 ΔCtsample , where the ΔCt (Δ Cycle Threshold) value of the sample was determined by subtracting the average Ct value of the X gene from the average Ct value of the TBP gene. The N X  values of the samples were subsequently normalized such that the median of the N X  values of the four normal breast samples would have a value of 1. The nucleotide sequences of the primers used for real-time RT-PCR amplification are described in Table 3. Total RNA extraction, cDNA synthesis and the PCR reaction conditions have been previously described in detail (Bieche et al., 2001, Cancer Res, Vol 61(4): 1652-1658). 
     Differences between two populations were judged significant at confidence levels&gt;95%, (P&lt;0.05), using Mann Whitney UTest (SEM) 
     ImmunoHistoChemistry 
     Metastatic biopsies from breast cancer patients were fixed in 4% formaldehyde in 0.1 M phosphate buffer, pH 7.2, and embedded in paraffin. Bone specimens were decalcified either with a solution of ethylenediaminetetraacetic acid (EDTA) and hydrochloric acid (Decalcifier II, Labonord) or with a solution of formalin (20%) and nitric acid (5%). Sections were cut using a Reichert-Jung 1150/Autocut microtome. Slide-mounted tissue sections (4 μm thick) were deparaffinized in xylene and hydrated serially in 100%, 95%, and 80% ethanol. Endogenous peroxidases were quenched in 3% H 2 O 2  in PBS for 1 hour, then slides were incubated with the indicated primary antibodies overnight at 4° C. Sections were washed three times in PBS, and antibody binding was revealed using the Ultra-Vision Detection System anti-Polyvalent HRP/DAB kit according to the manufacturer&#39;s instructions (Lab Vision). Finally, the slides were counterstained with Mayer&#39;s hematoxylin and washed in distilled water. 
     The anti-OMD and the anti-IBSP antibodies were kindly provided respectively by Dick Heinegard (Department of Experimental Medical Science, Lund University), Sweden and L.W. Fisher (National Institute of Dental Craniofacial Research, NIH, Bethesda, Md., USA). The anti-KIND1 and anti-TOP1 antibodies were purchased from Abcam, the anti-MMP-9 from Chemicon, and anti-DSC2 antibody from Progen respectively. 
     Example 1 
     Identification of Differentially Expressed Genes 
     We compared the transcriptional profiles of human breast cancer metastases from the four main target organs of relapse: bone, lung, liver and brain. Therefore, using microarray gene expression data (Affymetrix U133 Plus 2.0 chips), we examined 23 metastatic samples obtained from surgery. 
     To identify genes that were specifically expressed in each of the 4 metastatic organs, we performed one-versus-all (OVA) class comparisons to distinguish two known subgroups. We used the following combinations: 6 bone metastases versus all 17 others (non-bone metastases), 5 lung metastases versus 18 others, 6 liver metastases versus 17 others and 4 brain metastases versus 19 others. Gene expressions between two defined groups were compared by use of a univariate t-test, in which the critical p-value was set at 10 −4 . 
     After applying filtering criteria as described in Materials and Methods, we identified 4 gene lists corresponding to the genes differentially expressed in bone metastases (325 probes representing 276 genes), lung metastases (28 probes representing 23 genes), liver metastases (114 probes representing 83 genes) and brain metastases (133 probes representing 123 genes) (Table 1). Among the 600 identified probes (representing 505 genes), 77% were upregulated and 23% were downregulated. The bone and brain metastasis associated genes were downregulated in approximately 30% of the cases whereas the lung and liver metastasis associated genes were downregulated in about 5%. The 20 highest-ranking genes for each organ specific metastasis are illustrated in Table 2. 
     In order to validate at the protein level the observations made at the RNA level, we proceeded to immunohistochemistry analyses of several organ-specific metastatic gene products: DSC2 and KIND1 associated to lung metastasis and TOP1 corresponding to the brain metastatic process. As expected, proteins were highly expressed most exclusively by metastatic cells. KIND1 and TOP1 are highly and homogeneously expressed by metastatic cells, whereas DSC2 is principally highly expressed by metastatic cells present on the edge of the tumor, suggesting the presence of a cross talk with lung cells. 
     1.1. Main Biological Processes Involving Organ-Specific Metastasis Associated Genes 
     All the differentially expressed genes associated to the four sites of relapse were mapped to the Gene Ontology database. Among the 505 genes tested, 326 were annotated for the “Gene Ontology Biological Process Description”. The descriptions were classified in major biological processes (i.e., apoptosis, cell adhesion, cell cycle, cell signaling, cytoskeleton organization, RNA processing, transcription regulation) to determine whether certain processes were highly represented. Thereby, we observed that the “cell adhesion” related genes were represented in 4 out of 15 (26.6%) annotations in the lung metastasis list. For the liver and brain metastasis associated genes the “transcription regulation” was the most represented description in 21/58 (32.2%) and 20/63 (31.7%) respectively. In the bone metastasis gene list, the genes related to “cell signaling” were the most frequently found (61/190, i.e. 32.1%). In addition, as previously described, the bone metastasis associated genes contains high proportion of genes involved in immune response (Smid et al., 2006,). Highly represented annotations in each of the organ-specific metastatic gene list might point to particular biological processes, which are potentially linked to the site of relapse. 
     Among the “known” proteins identified, several have already been involved in cancer progression and/or metastatic phenotypes, such as the genes PTEN, PERP, PDGFRA, TBX3 (Attardi et al., 2000; Petrocelli et al., 2001; Rowley et al., 2004; Oliveira et al., 2005; Jechlinger et al., 2006). Among the liver metastasis associated genes, WHSC1L1 and LETM2 are of particular interest since they have been described as coamplified in lung cancer. Their upregulation is probably due to a genetic event in cancer cells (Tonon et al, 2005). The brain metastasis associated gene HOXB13 overexpression was recently associated with the clinical outcome in breast cancer patients (Ma et al., 2006). Moreover, among the bone metastasis associated genes, MFNG encodes Manic Fringe protein which modulates the Notch signaling pathway. This pathway has been reported to be involved in bone metastasis of prostate cancer (Zayzafoon et al, 2003), while TNFAIP8L2 and CSF-1 could be implicated in the enhancement of osteoclast formation and activity typically observed in breast cancer bone metastases. 
     1.2. Interaction with the Microenvironment in the Case of Bone Metastasis: Osteomimicry 
     Among the genes that were found differentially expressed in bone metastases but that were removed by our filtering criteria to avoid host-tissue genes (due to contamination), we identified several genes known to be expressed by cells of the osteoblastic lineage such as bone sialoprotein (IBSP) and osteocalcin (BGLAP) noncollagenous bone matrix proteins. We observed that metastatic breast cancer cells localized in bone consistently showed a strong immunoreactivity to IBSP, MMP9 and OMD in the majority of the samples analyzed. This observation is consistent with previous reports indicating that breast and prostate cancer cells metastasizing to bone express bone-related proteins (Koeneman 1999, Waltregny, 2000, Huang 2005). This phenomenon, named &lt;&lt;osteomimicry &gt;&gt;, could explain the propensity of osteotropic cancer cells to metastasize to the skeleton (Koeneman 1999). 
     1.3. Organ-Specific Metastatic Signature 
     The genes differentially expressed in the 4 target organs (Table 2) were then analyzed to define an organ-specific metastatic signature. Among these genes, 56 were tested by quantitative RT-PCR on a series of 29 breast cancer metastases consisting of 19 distant relapses already used for microarray analysis (4 bone metastases, 5 lung metastases, 6 liver metastases, 4 brain metastases) and 10 additional samples (1 bone metastasis, 3 lung metastases, 2 liver metastases and 4 skin metastases). 
     Thirty one genes (55%) passed the comparison criteria (OVA comparison, Mann Whitney U test, p value&lt;0.05) (supplementary table 3). The combination of these validated genes was evaluated as the organ-specific metastatic signature by hierarchical clustering. As shown by the dendrogram, the signature clearly separated the different metastatic classes. Remarkably, the bone metastases cluster seemed separated from the soft tissue metastases clusters. Our restricted “31-gene signature” showed similar patterns than the 80 highest-ranking genes (data not shown). 
     1.4. Predictive value of the organ-specific metastatic signature 
     The actual assumption is that primary tumors may already contain a gene expression profile that is strongly predictive of metastasis and in addition, tumor cells could also display a tissue-specific expression profile predicting the site of metastasis. To test this hypothesis, a series of publicly available microarray data relative to a cohort of 82 breast cancer patients with follow up (especially site of relapse) was analyzed (Minn et al, 2005a). In this series, 27 tumors relapsed, mainly in bone or lungs. Therefore, our identified lung- and bone-metastasis associated genes (only 6 and 10 genes respectively present on U133A chips) were used to cluster the 27 relapsing tumors (data not shown). We observed, in both cases, that many genes were expressed in the same way in relapsing tumors as the corresponding relapses. For example, genes upregulated or downregulated in bone metastases presented respectively higher or lower expression in breast tumor relapsing to bone than in those relapsing elsewhere. 
     Furthermore, primary tumors that highly express these bone metastasis genes seemed more susceptible to relapse to bone (p=0.082, χ 2  test). In the same way, primary tumors that highly express these lung metastasis genes were significantly more susceptible to relapse to lung (p=0.002, χ 2  test) ( FIG. 1 ). 
     Finally, we evaluated the predictive value of our organ-specific signature on the large cohort of 82 primary tumors. The organ-specific metastatic signature (represented by only 25 probes present on U133A chips) allowed a classification of those tumors within 3 main clusters corresponding to tumors giving rise mainly to lung metastases, bone metastases and no metastasis ( FIG. 2 ). 
     Kaplan Meier analyses were performed to assess the prognostic value of the signature with respect to organ-specific-metastasis-free survival. Patients with tumors expressing lung metastasis genes (cluster #1) had worse lung-metastasis-free survival (p=0.00066) but not bone-metastasis-free survival (data not shown). Patients with tumors expressing bone metastasis genes (cluster #2) showed a tendency to have a worst bone-metastasis free survival (p=0.12), and the patients included in the cluster #3 (tumors expressing neither bone nor lung metastasis genes) had a better metastasis free survival. 
     To confirm these results, we performed an analysis of the expression of the organ-specific metastatic signature by quantitative RT-PCR in an independent cohort of 35 patients. These patients were treated at Centre René Huguenin, did not receive chemotherapy and did all present relapses to bone or lung. Tumors that highly express lung metastasis genes (7 genes) significantly relapsed more to lung (p=0.04, χ 2  test). Patients who presented these latter tumors had a significantly worst lung metastasis free survival (p=0.00043, 10 years after diagnosis of the primary tumor. However, tumors that express bone metastasis genes did not relapsed more to bone (data not shown). 
     Examples 3 to 6 
     A. Materials and Methods of Examples 3 to 6 
     A.1. Patients and Samples 
     The study was performed according to the local ethical regulations. We first studied the transcriptome of 23 metastases (5 lung, 6 liver, 4 brain, 2 skin and 6 osteolytic bone metastases) from breast cancer patients that undergone surgery (n=22). Then, additional 10 samples were used for RT-PCR validation (3 lung, 2 liver, 4 skin and 1 bone metastases) (n=10). All metastatic samples were obtained from University of L&#39;Aquila (L&#39;Aquila, Italy), IDIBELL (Barcelona, Spain) and Centre René Huguenin (CRH, Saint-Cloud, France). Normal-tissue RNA pools were prepared from 6 bone (L&#39;Aquila), 4 brain (IDIBELL), and at least 5 breast, lung, and liver normal samples purchased from Clontech (Palo Alto, USA), Biochain (Hayward, USA) and Invitrogen (Frederick, USA). 
     A series of 72 primary breast tumors (“CRH cohort”) was specifically selected from patients with node-negative breast cancer treated at the Centre René Huguenin, and who did not receive systemic neoadjuvant or adjuvant therapy (median follow-up of 132 months, range 22.6 to 294 months). During 10 years of follow-up, 38 patients developed distant metastases. Eleven of these patients developed lung metastases as the first site of distant relapse. 
     We also analyzed 3 independent breast tumor series; the “MSK” (n=82), “EMC” (n=344) and “NKI” (n=295) cohorts described in detail elsewhere (4, 6, 12, 14) for which microarray data can be freely downloaded from the NCBI website. Briefly, “EMC” and “NKI” cohorts consist of early stage breast cancers 100% and 50% lymph node-negative, respectively whereas “MSK” series is consisting of locally advanced tumors, 66% node-positives). 
     Finally, paraffin-embedded sections of lung metastases and paired breast tumors were obtained from Liege University (Belgium) and from Centre Rene Huguenin (France) to perform immunohistological analyses. 
     A.2. Gene Expression Analysis 
     For microarray analysis, sample labeling, hybridization, and staining were carried out as previously described (Jackson et al., 2005). Human Genome U133 Plus 2.0 arrays were scanned in an Affymetrix GeneChip scanner 3000 at 570 nm. The 5′/3′ GAPDH ratios averaged 3.5. The average background, noise average, % Present calls and average signal of Present calls were similar with all the arrays used in this experiment. 
     For quantitative RT-PCR analysis, we used cDNA synthesis and PCR conditions described in detail elsewhere (34). All PCR reactions were performed with an ABI Prism 7700 Sequence Detection System (Perkin-Elmer Applied Biosystems) and the SYBR Green PCR Core Reagents kit (Perkin-Elmer Applied Biosystems). TATA-box-binding protein (TBP) transcripts were used as an endogenous RNA control, and each sample was normalized on the basis of its TBP content (Bieche et al., 2001). 
     A.3. Immunohistochemistry 
     Biopsy specimens of primary tumors and matching lung metastases from breast cancer patients were fixed and embedded in paraffin. Sections 4 μm thick were deparaffinized in xylene and hydrated in serial ethanol concentrations. Endogenous peroxidases were quenched in PBS containing 3% H 2 O 2  for 1 hour, then the slides were incubated with the indicated primary antibodies overnight at 4° C. Sections were washed, and antibody binding was revealed with the Ultra-Vision Detection System Anti-Polyvalent HRP/DAB kit (Lab Vision). Finally, the slides were counterstained with Mayer&#39;s hematoxylin and washed in distilled water. The anti-FERMT1 and anti-DSC2 antibodies were purchased from Abcam (Cambridge, USA) and Progen (Queensland, Australia), respectively. 
     A.4. Statistical analysis 
     Microarray expression profiles were analyzed with BRB Array tools, version 3.3beta3 developed by Richard Simon and Amy Peng Lam (http://linus.nci.nih.gov/BRB-ArrayTools.html). Expression data were collated as CEL files, and calculation of Affymetrix probe set summaries and quantile normalization were done using the RMA function of Bioconductor. Univariate t tests were used to identify genes differentially expressed between 5 lung metastases and 18 non lung metastases (6 bone, 4 brain, 6 liver, and 2 skin). Differences were considered statistically significant if the p value was less than 0.0001. This stringent threshold was used to limit the number of false-positives. 
     Several selection filters were used to refine the lung metastasis-related gene set. First, we filtered potential host-tissue genes characterized by a 1.5-fold higher expression level in normal lung tissue than in each of the other three normal tissue pools (bone, liver and brain). These genes were considered as potentially expressed by contaminating host tissue. Second, genes with geometric mean intensities below 25 in both lung and non lung metastases were removed. Finally, probes aligned against human genome (using Blast software from the NCBI website) not recognizing any transcripts were excluded. 
     Genes of interest were mapped between different platforms by using Unigene identifiers. The individual breast cancer series were then analyzed with the same probes when possible. To determine whether gene expression profiles were able to define low- and high-lung metastasis risk populations in the CRH cohort, the six-gene signature was used to create a risk index defined as a linear combination of the gene expression values. The distribution of risk index values was examined to determine the optimal cut point at the 75 th  percentile to distinguish high and low risk in the CRH series. The risk index function and the high/low risk cutoff point were then applied to the MSK, EMC, NKI and combined cohorts. 
     Survival times were estimated by the Kaplan-Meier method, and the significance of differences was determined with the log-rank test. Multivariate analyses were performed using the Cox proportional hazards regression model. 
     Example 3 
     Identification of Lung Metastasis-Associated Genes 
     We first performed a microarray analysis to compare the gene transcript profiles of 5 lung metastases and 18 metastases from other target organs (bone, liver, brain and skin), all obtained from breast cancer patients undergoing surgery. A class comparison was conducted based on a univariate t test, with a stringent p value of 10 −4 , to identify genes differentially expressed by the two tissue categories. 
     After applying filtering criteria (see Patients and Methods), we identified 21 differentially expressed genes (19 known and 2 unknown genes) (Table 5), mostly overexpressed in lung metastases. Only one gene, the tumor suppressor gene PTEN, was down-regulated. 
     To technically validate the differentially expressed genes, we examined the expression of the highest-ranking genes by quantitative RT-PCR using 19 samples analyzed by microarray (4 had no more RNA available) and 10 additional breast cancer metastases including 3 lung relapses. This validation step led to the selection of 7 genes showing a significant variation of expression, namely DSC2, HORMAD1, TFCP2L1, UGT8, ITGB8, ANP32E and FERMT1 (Table 5). 
     Furthermore, to verify that these observed differentially expressed profiles were due to the metastatic samples but not to differential expression of adjacent host tissues, we evaluated the protein expression for 2 representative genes: DSC2 and FERMT1 (corresponding to the upper and lower p values, Table 5). Strong immunoreactivity was detected for both proteins, almost exclusively in the tumor cells, and not in the surrounding pulmonary tissue. 
     The characterized genes were mapped into the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases to investigate their functions and biological processes (Table 5). Interestingly, the lung metastasis-related genes showed an overrepresentation of membrane-bound molecules mainly involved in cell adhesion and/or signal transduction (DSC2, UGT8, ITGB8, FERMT1). Very little is known on the other identified genes (HORMAD1, TFCP2L1 and ANP32E). None of these proteins have been previously shown to be specifically involved in metastasis. 
     Example 4 
     Development of a Predictor of Selective Breast Cancer Failure to the Lungs 
     To determine whether the 7 lung metastasis-associated genes could already be expressed in primary breast tumor cells and whether they could be predictive of a higher risk of lung metastasis, we analyzed by qRT-PCR their expression patterns in a series of 5 normal breast tissue samples, 6 breast cancer cell lines (MCF7, T47D, SKBR3, MDA-MB-231, MDA-MB-361 and MDA-MB-435) and 44 primary breast tumors. All lung-metastasis-associated genes were expressed in tissues of mammary origin except HORMAD1 that showed very weak to no expression in all normal breast, all cell lines and a majority of primary tumors (Ct&lt;35). Therefore, HORMAD1 was not considered in our attempt to establish a lung metastasis signature. 
     The 6 remaining genes (DSC2, TFCP2L1, UGT8, ITGB8, ANP32E and FERMT1) were used to develop a gene signature predictive of a higher risk of lung metastasis. We studied a cohort of 72 lymph-node-negative patients specifically selected on the basis of the treatments and metastatic outcomes: the CRH cohort. All 72 patients had not received neoadjuvant or adjuvant therapy. This meant that the potential prognostic impact of the “lung-metastasis classifier” would not be influenced by factors related to systemic treatment. Thirty-eight patients had developed distant metastases within 10 years (including 11 with lung metastases) and 34 patients remained free of disease after their initial diagnosis for a period of at least 10 years (Table 6). 
     The primary tumors were then assigned to a high-risk group or a low-risk group, with respect to lung metastasis, according to the risk index calculated on the basis of the six-gene signature. The lung metastasis risk index was defined as the linear combination of the expression values of the 6 genes and the appropriate cutoff point was set at the 75 th  percentile. Tumors expressing high levels of the risk index metastasized significantly more frequently to the lungs than did the other tumors (p=0.04, χ 2  test,  FIG. 3A ). In addition, patients with such tumors had significantly shorter lung-metastasis-free survival (p=0.008  FIG. 3B ). The six-gene signature did not correlate with the risk of bone metastasis ( FIG. 3C ) or liver metastasis ( FIG. 3D ). 
     Example 5 
     Validation of the Predictive Ability of the Six-Gene Signature 
     To validate the predictive value of the six-gene lung metastasis signature, we analyzed expression profiles of 3 independent cohorts of breast cancer patients which microarray data are publicly available (Wang et al., 2005; Van de Vijver, 2002; Minn et al., 2005, Minn et al., 2007). These 3 datasets correspond to 2 large cohorts of early stage breast cancer patients (“NKI” and “EMC” series of 295 and 344 patients, respectively) and a more locally advanced cohort of breast cancers (the “MSK” cohort of 82 patients) (Wang et al., 2005; Van de Vijver, 2002; Minn et al., 2005, Minn et al., 2007). 
     Hierarchical clustering analysis was performed on all individual series. Within the 3 different cohorts, the six-gene signature discriminates a subgroup of breast tumors with a higher propensity to metastasize to the lungs (p=0.04, p=0.016 and p=0.014, χ 2  test, for MSK, EMC and NKI respectively). As representative results, the clustering of the MSK and NKI breast tumors have been performed. 
     The results of hierarchical clustering are only indicative. Thus, using the same procedure as for the CRH cohort, we evaluated the six-gene signature in the 3 independent cohorts. Patients assigned to the high-risk group had significantly shorter lung-metastasis-free survival in all cases (p=0.004, 0.001 and 0.039 for MSK, EMC and NKI series respectively,  FIG. 4 ), whereas there was no difference in bone-metastasis-free survival. It is noteworthy that there is a fewer discrimination in NKI cohort, probably due to the consideration of only 5 genes of the signature since one gene (ANP32E) was not present in the corresponding chips. Finally, the Kaplan-Meier analysis was also performed on the combined cohort and resulted in a highly significant correlation of the six-gene signature with the outcome of breast cancer patient with regard to lung metastasis (n=721, p&lt;10 −5 ). 
     Example 6 
     Correlation to standard Clinico-Pathological Variables and Other Prognostic Signatures 
     We evaluated whether the six-gene signature provided additional prognostic information that may not be obtained by other models and/or standard markers. First, we analyzed the NKI series (for which the complete clinical data were documented) for the main prognostic molecular signatures reported for breast cancers. Consistent with previous reports, the primary breast tumors expressing the six-gene signature also expressed other poor-prognosis molecular markers (Kang et al., 2003; Minn et al., 2007). The tumors of patients at risk for lung metastasis as defined by the six-gene signature mostly were of poor prognosis on the basis of standard pathological parameters (62% ER-negative and 70% grade 3) and previously reported poor-prognosis signatures as the 70-gene signature (van&#39;t Veer et al., 2002; van de Vijver et al., 2002), the wound-healing signature (Chang et al., 2005; Chang et al., 2005) and the basal-like molecular subtype (23, 24) (80%, 89%, and 58% respectively). 
     In addition, when analyzing the clinicopathological variables available for each of the cohorts of breast cancer patients, we found no difference between the high- and low-risk groups with respect to age, lymph node status or primary tumor size, whereas most high-risk patients and their tumors appeared to be hormone receptor-negative and grade 3. 
     To ensure that the six-gene classifier improved risk stratification independently of these standard clinical parameters, we performed a multivariate Cox proportional-hazards analysis on the combined cohort (n=721) (only estrogen-receptor and lymph node status parameters were available for all patients, Table 7). The Cox model showed that the six-gene signature and estrogen receptor status were independent predictors of lung metastasis (p=0.01 and 0.04 respectively). The six-gene signature is a significant predictor of lung metastasis in breast cancer. It added new and important prognostic information beyond that provided by ER and lymph node status. 
     Finally, we compared the predictive value of our lung metastasis signature to the one derived from the MDA-MB-231 mouse model (LMS) (Minn et al., 2007). These two signatures are defined by expression patterns of distinct sets of genes with no overlap. When evaluated on the same series of 721 samples, we observe that despite their different derivations, the signatures gave overlapping and consistent predictions outcome. Each signature assigned the same patients to the high or low risk groups of breast cancer lung metastasis. Indeed, the two models have high level of concordance in their predictions of lung metastasis. Almost all tumors identified as LMS were also classified as having the six-gene signature. LMS and our six-gene signature showed 85% agreement in outcome classification of breast cancer patients with respect to lung metastasis (Kappa coefficient=0.57). These results suggest that even though there are no gene overlap and different biological models were used, the outcome predictions still are similar, probably because they track common set of biological characteristics conferring the organ-specific metastatic phenotypes. 
     Thus, to determine whether the use of the two models together would result in a better model than the use of any one alone, we derived a single model based on the common findings of the 2 models separately. The performance of this model according to the Kaplan-Meier analysis was noticeably better than each of the 2 models ( FIG. 5B ) demonstrating that gene signatures derived from 2 distinct approaches can be complementary, as recently reported for the 70-gene and WR signatures corresponding to the “top-down” and “bottom-up” strategies respectively (Chang et al., 2005). 
     Further, as shown in  FIG. 6 , primary that highly express eleven-gene bone metastasis signature are more susceptible to relapse to bone. 
     Also, Table 8 shows the highets ranking genes obtained from a class comparison of bone and non-bone metastases of breast cancer. 
     REFERENCES 
     
         
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Nature. 2005 Jul. 28; 436(7050):518-24.   Minn, A. J., Gupta, G. P., Padua, D., Bos, P., Nguyen, D. X., Nuyten, D., Kreike, B., Zhang, Y., Wang, Y., lshwaran, H., Foekens, J. A., van de Vijver, M. &amp; Massague, J. (2007) Proc Natl Acad Sci USA 104, 6740-5.   Minn A J, Kang Y, Serganova I, Gupta G P, Giri D D, Doubrovin M, Ponomarev V, Gerald W L, Blasberg R, Massague J. Distinct organ-specific metastatic potential of individual breast cancer cells and primary tumors. J Clin Invest. 2005 January; 115(1):44-55   Oliveira A M, Ross J S, Fletcher J A. Tumor suppressor genes in breast cancer: the gatekeepers and the caretakers. Am J Clin Pathol. 2005 124 Suppl:S16-28. Review.   Petrocelli T, Slingerland J M. PTEN deficiency: a role in mammary carcinogenesis. Breast Cancer Res. 2001; 3(6):356-60. Review.   Ramaswamy S, Ross K N, Lander E S, Golub T R. A molecular signature of metastasis in primary solid tumors. Nat Genet. 2003 January; 33(1):49-54.   Rehn A P, Chalk A M, Wendel M. Differential regulation of osteoadherin (OSAD) by TGF-beta1 and BMP-2. Biochem Biophys Res Commun. 2006 Oct. 27; 349(3):1057-64.   Roodman G D. Mechanism of bone metastases. N Eng J Med 2004; 350:1655-64.   Rowley M, Grothey E, Couch F J. The role of Tbx2 and Tbx3 in mammary development and tumorigenesis. J Mammary Gland Biol Neoplasia. 2004 April; 9(2):109-18. Review   Sharp J A, Waltham M, Williams E D, Henderson M A, Thompson E W. Transfection of MDA-MB-231 human breast cancer cells with bone sialoprotein (BSP) stimulates growth of primary and secondary tumors in nude mice. Clin Exp Metastasis 2004; 21:19-29.   Smid M, Wang Y, Klijn J G, Sieuwerts A M, Zhang Y, Atkins D, Martens J W, Foekens J A. Genes associated with breast cancer metastatic to bone. J Clin Oncol. 2006 May 20; 24(15):2261-7   Steeg P S. Tumor metastasis: mechanistic insights and clinical challenges. Nat Med. 2006 August; 12(8):895-904.   Tonon G, Wong K K, Maulik G, Brennan C, Feng B, Zhang Y, Khatry D B, Protopopov A, You M J, Aguirre A J, Martin E S, Yang Z, Ji H, Chin L, Depinho R A. High-resolution genomic profiles of human lung cancer. Proc Natl Acad Sci USA. 2005 Jul. 5; 102(27):9625-30.   van de Vijver, M. J., He, Y. D., van&#39;t Veer, L. J., Dai, H., Hart, A. A., Voskuil, D. W., Schreiber, G. J., Peterse, J. L., Roberts, C., Marton, M. J., Parrish, M., Atsma, D., Witteveen, A., Glas, A., Delahaye, L., van der Velde, T., Bartelink, H., Rodenhuis, S., Rutgers, E. T., Friend, S. H. &amp; Bernards, R. (2002) N Engl J Med 347, 1999-2009.   van&#39;t Veer L J, Dai H, van de Vijver M J, He Y D, Hart A A, Mao M, Peterse H L, van der Kooy K, Marton M J, Witteveen A T, Schreiber G J, Kerkhoven R M, Roberts C, Linsley P S, Bernards R, Friend S H. Gene expression profiling predicts clinical outcome of breast cancer. Nature. 2002; 415:530-536.   Waltregny D, Bellahcene A, de Leval X, Florkin B, Weidle U, Castronovo V. Increased expression of bone sialoprotein in bone metastases compared with visceral metastases in human breast and prostate cancers. J Bone Miner Res. 2000 May; 15(5):834-43.   Wang Y, Klijn J G, Zhang Y, Sieuwerts A M, Look M P, Yang F, Talantov D, Timmermans M, Meijer-van Gelder M E, Yu J, Jatkoe T, Berns E M, Atkins D, Foekens J A. Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer. Lancet. 2005 February 19-25; 365(9460):671-9   Weigelt B, Hu Z, He X, Livasy C, Carey L A, Ewend M G, Glas A M, Perou C M, Van&#39;t Veer L J. Molecular portraits and 70-gene prognosis signature are preserved throughout the metastatic process of breast cancer. Cancer Res. 2005 Oct. 15; 65(20):9155-8.   Weigelt B, Peterse J L, van&#39;t Veer L J. Breast cancer metastasis: markers and models. Nat Rev Cancer. 2005 August; 5(8):591-602.   Yoneda T, Hiraga T. Cross-talk between cancer cells and bone microenvironment in bone metastasis. 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                 TABLE 1 
               
               
                   
                   
               
             
            
               
                   
                   
                 Geometric mean of 
                   
               
               
                   
                 Parametric p- 
                 intensities in 
                 ratio 
               
            
           
           
               
               
               
               
               
               
            
               
                 Probe Set 
                 Gene 
                 Gene Title 
                 value 
                 Bone 
                 Non_Bone 
               
               
                 BONE 
                 Symbol 
                 METASTASIS ASSOCIATED 
                 MARKERS 
                 metastases 
                 metastases 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                 221724_s_at 
                 CLEC4A 
                 C-type lectin domain family 4, 
                 p &lt; 0.000001 
                 55.9 
                 22.8 
                 2.45 
               
               
                   
                   
                 member A 
               
               
                 204153_s_at 
                 MFNG 
                 manic fringe homolog ( Drosophila ) 
                 p &lt; 0.000001 
                 92.7 
                 34.5 
                 2.69 
               
               
                 208922_s_at 
                 NXF1 
                 nuclear RNA export factor 1 
                 p &lt; 0.000001 
                 281.2 
                 174.6 
                 1.61 
               
               
                 227002_at 
                 FAM78A 
                 family with sequence similarity 78, 
                 p &lt; 0.000001 
                 91.2 
                 37.6 
                 2.43 
               
               
                   
                   
                 member A 
               
               
                 226245_at 
                 KCTD1 
                 potassium channel tetramerisation 
                 p &lt; 0.000001 
                 60.7 
                 199.2 
                 0.30 
               
               
                   
                   
                 domain containing 1 
               
               
                 227372_s_at 
                 BAIAP2L1 
                 BAI1-associated protein 2-like 1 
                 p &lt; 0.000001 
                 23.6 
                 245.8 
                 0.10 
               
               
                 206060_s_at 
                 PTPN22 
                 protein tyrosine phosphatase, non- 
                 p &lt; 0.000001 
                 64.3 
                 15.6 
                 4.12 
               
               
                   
                   
                 receptor type 22 (lymphoid) 
               
               
                 232523_at 
                 MEGF10 
                 multiple EGF-like-domains 10 
                 p &lt; 0.000001 
                 119.6 
                 11.1 
                 10.77 
               
               
                 222392_x_at 
                 PERP 
                 PERP, TP53 apoptosis effector 
                 p &lt; 0.000001 
                 215.2 
                 2340 
                 0.09 
               
               
                 211178_s_at 
                 PSTPIP1 
                 proline-serine-threonine phosphatase 
                 p &lt; 0.000001 
                 60.2 
                 20 
                 3.01 
               
               
                   
                   
                 interacting protein 1 
               
               
                 204236_at 
                 FLI1 
                 Friend □aematolo virus integration 1 
                 p &lt; 0.000001 
                 79.7 
                 16.6 
                 4.80 
               
               
                 213290_at 
                 COL6A2 
                 collagen, type VI, alpha 2 
                 p &lt; 0.000001 
                 99.2 
                 37.7 
                 2.63 
               
               
                 203547_at 
                 CD4 
                 CD4 molecule 
                 p &lt; 0.000001 
                 240.3 
                 91.6 
                 2.62 
               
               
                 205382_s_at 
                 CFD 
                 complement factor D (adipsin) 
                 p &lt; 0.000001 
                 601.4 
                 81.6 
                 7.37 
               
               
                 235593_at 
                 ZFHX1B 
                 zinc finger homeobox 1b 
                 p &lt; 0.000001 
                 35.6 
                 12.2 
                 2.92 
               
               
                 206120_at 
                 CD33 
                 CD33 molecule 
                 p &lt; 0.000001 
                 93.6 
                 40.2 
                 2.33 
               
               
                 214181_x_at 
                 LST1 
                 leukocyte specific transcript 1 
                 p &lt; 0.000001 
                 242 
                 62.5 
                 3.87 
               
               
                 219091_s_at 
                 MMRN2 
                 multimerin 2 
                 p &lt; 0.000001 
                 128.3 
                 43.4 
                 2.96 
               
               
                 1552667_a_at 
                 SH2D3C 
                 SH2 domain containing 3C 
                 p &lt; 0.000001 
                 48.3 
                 20.9 
                 2.31 
               
               
                 205326_at 
                 RAMP3 
                 receptor (calcitonin) activity modifying 
                 p &lt; 0.000001 
                 163 
                 83.8 
                 1.95 
               
               
                   
                   
                 protein 3 
               
               
                 221565_s_at 
                 FAM26B 
                 family with sequence similarity 26, 
                 p &lt; 0.000001 
                 164.5 
                 82 
                 2.01 
               
               
                   
                   
                 member B 
               
               
                 201234_at 
                 ILK 
                 integrin-linked kinase 
                 p &lt; 0.000001 
                 462.9 
                 208.5 
                 2.22 
               
               
                 219892_at 
                 TM6SF1 
                 transmembrane 6 superfamily 
                 p &lt; 0.000001 
                 107.4 
                 19.8 
                 5.42 
               
               
                   
                   
                 member 1 
               
               
                 226345_at 
                   
                 CDNA FLJ12853 fis, clone 
                 p &lt; 0.000001 
                 61.7 
                 200.1 
                 0.31 
               
               
                   
                   
                 NT2RP2003456 
               
               
                 225373_at 
                 C10orf54 
                 chromosome 10 open reading frame 
                 p &lt; 0.000001 
                 238.6 
                 77 
                 3.10 
               
               
                   
                   
                 54 
               
               
                 205200_at 
                 CLEC3B 
                 C-type lectin domain family 3, 
                 p &lt; 0.000001 
                 201.7 
                 37.9 
                 5.32 
               
               
                   
                   
                 member B 
               
               
                 204116_at 
                 IL2RG 
                 interleukin 2 receptor, gamma 
                 1.00E−06 
                 226 
                 69.2 
                 3.27 
               
               
                   
                   
                 (severe combined immunodeficiency) 
               
               
                 209721_s_at 
                 HOM-TES- 
                 hypothetical protein LOC25900, 
                 1.00E−06 
                 128.7 
                 62.8 
                 2.05 
               
               
                   
                 103 
                 isoform 3 
               
               
                 237861_at 
                 ZNF23 
                 Zinc finger protein 23 (KOX 16) 
                 1.00E−06 
                 48.6 
                 29.6 
                 1.64 
               
               
                 225649_s_at 
                 STK35 
                 serine/threonine kinase 35 
                 1.00E−06 
                 201.3 
                 542.1 
                 0.37 
               
               
                 217744_s_at 
                 PERP 
                 PERP, TP53 apoptosis effector 
                 2.00E−06 
                 48.6 
                 611.5 
                 0.08 
               
               
                 223583_at 
                 TNFAIP8L2 
                 tumor necrosis factor, alpha-induced 
                 2.00E−06 
                 48.5 
                 23 
                 2.11 
               
               
                   
                   
                 protein 8-like 2 
               
               
                 205779_at 
                 RAMP2 
                 receptor (calcitonin) activity modifying 
                 2.00E−06 
                 122.3 
                 51.2 
                 2.39 
               
               
                   
                   
                 protein 2 
               
               
                 201809_s_at 
                 ENG 
                 endoglin (Osler-Rendu-Weber 
                 2.00E−06 
                 330.6 
                 126.4 
                 2.62 
               
               
                   
                   
                 syndrome 1) 
               
               
                 223717_s_at 
                 ACRBP 
                 acrosin binding protein 
                 2.00E−06 
                 53.1 
                 30.3 
                 1.75 
               
               
                 228258_at 
                 TBC1D10C 
                 TBC1 domain family, member 10C 
                 2.00E−06 
                 112.8 
                 42.4 
                 2.66 
               
               
                 221637_s_at 
                 C11orf48 
                 chromosome 11 open reading frame 
                 2.00E−06 
                 138.7 
                 297.8 
                 0.47 
               
               
                   
                   
                 48 
               
               
                 201323_at 
                 EBNA1BP2 
                 EBNA1 binding protein 2 
                 3.00E−06 
                 66.4 
                 190.6 
                 0.35 
               
               
                 229099_at 
                   
                 CDNA clone MGC: 87549 
                 3.00E−06 
                 49.2 
                 124.5 
                 0.40 
               
               
                   
                   
                 IMAGE: 30347387 
               
               
                 205133_s_at 
                 HSPE1 
                 heat shock 10 kDa protein 1 
                 3.00E−06 
                 338.6 
                 1156.2 
                 0.29 
               
               
                   
                   
                 (chaperonin 10) 
               
               
                 202177_at 
                 GAS6 
                 growth arrest-specific 6 
                 3.00E−06 
                 248.7 
                 60.7 
                 4.10 
               
               
                 208018_s_at 
                 HCK 
                 hemopoietic cell kinase 
                 3.00E−06 
                 253.1 
                 46.3 
                 5.47 
               
               
                 204430_s_at 
                 SLC2A5 
                 solute carrier family 2 (facilitated 
                 3.00E−06 
                 124 
                 22.5 
                 5.51 
               
               
                   
                   
                 glucose/fructose transporter), 
               
               
                   
                   
                 member 5 
               
               
                 225562_at 
                 RASA3 
                 RAS p21 protein activator 3 
                 3.00E−06 
                 126.2 
                 63.3 
                 1.99 
               
               
                 1554628_at 
                 ZNF57 
                 zinc finger protein 57 
                 3.00E−06 
                 18.3 
                 57.6 
                 0.32 
               
               
                 202665_s_at 
                 WASPIP 
                 Wiskott-Aldrich syndrome protein 
                 3.00E−06 
                 104.1 
                 43.8 
                 2.38 
               
               
                   
                   
                 interacting protein 
               
               
                 204678_s_at 
                 KCNK1 
                 potassium channel, subfamily K, 
                 3.00E−06 
                 20.2 
                 101.9 
                 0.20 
               
               
                   
                   
                 member 1 
               
               
                 214847_s_at 
                 GPSM3 
                 G-protein signalling modulator 3 
                 3.00E−06 
                 115.2 
                 57 
                 2.02 
               
               
                   
                   
                 (AGS3-like,  C. elegans ) 
               
               
                 230800_at 
                 ADCY4 
                 adenylate cyclase 4 
                 4.00E−06 
                 136.9 
                 82.2 
                 1.67 
               
               
                 211133_x_at 
                 LILRB2/ 
                 leukocyte immunoglobulin-like 
                 4.00E−06 
                 189.6 
                 117.5 
                 1.61 
               
               
                   
                 LILRB3 
                 receptor, subfamily B (with TM and 
               
               
                   
                   
                 ITIM domains), member 2/leukocyte 
               
               
                   
                   
                 immunoglobulin-like receptor, 
               
               
                   
                   
                 subfamily B (with TM and ITIM 
               
               
                   
                   
                 domains), member 3 
               
               
                 215051_x_at 
                 AIF1 
                 allograft inflammatory factor 1 
                 4.00E−06 
                 644.5 
                 213.6 
                 3.02 
               
               
                 202663_at 
                 WASPIP 
                 Wiskott-Aldrich syndrome protein 
                 4.00E−06 
                 53.9 
                 19.4 
                 2.78 
               
               
                   
                   
                 interacting protein 
               
               
                 207738_s_at 
                 NCKAP1 
                 NCK-associated protein 1 
                 4.00E−06 
                 426.5 
                 874.1 
                 0.49 
               
               
                 228094_at 
                 AMICA1 
                 adhesion molecule, interacts with 
                 4.00E−06 
                 110.4 
                 43.7 
                 2.53 
               
               
                   
                   
                 CXADR antigen 1 
               
               
                 209482_at 
                 POP7 
                 processing of precursor 7, 
                 4.00E−06 
                 162.8 
                 370.4 
                 0.44 
               
               
                   
                   
                 ribonuclease P subunit ( S. cerevisiae ) 
               
               
                 204220_at 
                 GMFG 
                 glia maturation factor, gamma 
                 4.00E−06 
                 457.8 
                 108.8 
                 4.21 
               
               
                 226074_at 
                 PPM1M 
                 protein phosphatase 1M (PP2C 
                 4.00E−06 
                 102.5 
                 56.6 
                 1.81 
               
               
                   
                   
                 domain containing) 
               
               
                 226056_at 
                 CDGAP 
                 Cdc42 GTPase-activating protein 
                 4.00E−06 
                 34.8 
                 18.7 
                 1.86 
               
               
                 213095_x_at 
                 AIF1 
                 allograft inflammatory factor 1 
                 4.00E−06 
                 630.7 
                 181.1 
                 3.48 
               
               
                 1552318_at 
                 GIMAP1 
                 GTPase, IMAP family member 1 
                 5.00E−06 
                 25.6 
                 12.6 
                 2.03 
               
               
                 227780_s_at 
                   
                   
                 5.00E−06 
                 152 
                 66.7 
                 2.28 
               
               
                 232543_x_at 
                 ARHGAP9 
                 Rho GTPase activating protein 9 
                 5.00E−06 
                 209.6 
                 57.9 
                 3.62 
               
               
                 220023_at 
                 APOB48R 
                 apolipoprotein B48 receptor 
                 5.00E−06 
                 68.1 
                 33.9 
                 2.01 
               
               
                 225314_at 
                 OCIAD2 
                 OCIA domain containing 2 
                 5.00E−06 
                 160.7 
                 709.5 
                 0.23 
               
               
                 204359_at 
                 FLRT2 
                 fibronectin leucine rich 
                 5.00E−06 
                 259.5 
                 36.6 
                 7.09 
               
               
                   
                   
                 transmembrane protein 2 
               
               
                 229686_at 
                 P2RY8 
                 purinergic receptor P2Y, G-protein 
                 5.00E−06 
                 72.5 
                 33.3 
                 2.18 
               
               
                   
                   
                 coupled, 8 
               
               
                 221215_s_at 
                 RIPK4 
                 receptor-interacting serine-threonine 
                 5.00E−06 
                 47.5 
                 169.1 
                 0.28 
               
               
                   
                   
                 kinase 4 
               
               
                 208981_at 
                 PECAM1 
                 platelet/endothelial cell adhesion 
                 5.00E−06 
                 440.2 
                 134.3 
                 3.28 
               
               
                   
                   
                 molecule (CD31 antigen) 
               
               
                 204265_s_at 
                 GPSM3 
                 G-protein signalling modulator 3 
                 6.00E−06 
                 370.9 
                 141 
                 2.63 
               
               
                   
                   
                 (AGS3-like,  C. elegans ) 
               
               
                 223303_at 
                 URP2 
                 UNC-112 related protein 2 
                 6.00E−06 
                 294.1 
                 83.2 
                 3.53 
               
               
                 205504_at 
                 BTK 
                 Bruton agammaglobulinemia tyrosine 
                 6.00E−06 
                 126.9 
                 48.5 
                 2.62 
               
               
                   
                   
                 kinase 
               
               
                 228931_at 
                   
                   
                 6.00E−06 
                 48.2 
                 135.6 
                 0.36 
               
               
                 210784_x_at 
                 LILRB2/ 
                 leukocyte immunoglobulin-like 
                 6.00E−06 
                 191.6 
                 109.3 
                 1.75 
               
               
                   
                 LILRB3 
                 receptor, subfamily B (with TM and 
               
               
                   
                   
                 ITIM domains), member 2/leukocyte 
               
               
                   
                   
                 immunoglobulin-like receptor, 
               
               
                   
                   
                 subfamily B (with TM and ITIM 
               
               
                   
                   
                 domains), member 3 
               
               
                 214574_x_at 
                 LST1 
                 leukocyte specific transcript 1 
                 6.00E−06 
                 213.9 
                 71.9 
                 2.97 
               
               
                 230925_at 
                 APBB1IP 
                 amyloid beta (A4) precursor protein- 
                 6.00E−06 
                 661 
                 167.2 
                 3.95 
               
               
                   
                   
                 binding, family B, member 1 
               
               
                   
                   
                 interacting protein 
               
               
                 204192_at 
                 CD37 
                 CD37 molecule 
                 6.00E−06 
                 104.9 
                 19.2 
                 5.46 
               
               
                 206868_at 
                 STARD8 
                 START domain containing 8 
                 6.00E−06 
                 99 
                 57.6 
                 1.72 
               
               
                 229367_s_at 
                 GIMAP6 
                 GTPase, IMAP family member 6 
                 6.00E−06 
                 136.7 
                 33 
                 4.14 
               
               
                 203957_at 
                 E2F6 
                 E2F transcription factor 6 
                 7.00E−06 
                 63.2 
                 148.9 
                 0.42 
               
               
                 230805_at 
                   
                 Transcribed locus, strongly similar to 
                 6.00E−06 
                 71 
                 35.6 
                 1.99 
               
               
                   
                   
                 XP_511906.1 PREDICTED: similar to 
               
               
                   
                   
                 KIAA0612 protein [Pan troglodytes] 
               
               
                 205400_at 
                 WAS 
                 Wiskott-Aldrich syndrome (eczema- 
                 7.00E−06 
                 52 
                 27.8 
                 1.87 
               
               
                   
                   
                 thrombocytopenia) 
               
               
                 38964_r_at 
                 WAS 
                 Wiskott-Aldrich syndrome (eczema- 
                 7.00E−06 
                 394.8 
                 239.5 
                 1.65 
               
               
                   
                   
                 thrombocytopenia) 
               
               
                 204674_at 
                 LRMP 
                 lymphoid-restricted membrane 
                 7.00E−06 
                 135.4 
                 56 
                 2.42 
               
               
                   
                   
                 protein 
               
               
                 211654_x_at 
                 HLA-DQB1 
                 major histocompatibility complex, 
                 7.00E−06 
                 476.5 
                 121.6 
                 3.92 
               
               
                   
                   
                 class II, DQ beta 1 
               
               
                 226879_at 
                 HVCN1 
                 hydrogen voltage-gated channel 1 
                 7.00E−06 
                 127.3 
                 65.9 
                 1.93 
               
               
                 203622_s_at 
                 LOC56902 
                 putatative 28 kDa protein 
                 7.00E−06 
                 128 
                 297.5 
                 0.43 
               
               
                 204957_at 
                 ORC5L 
                 origin recognition complex, subunit 5- 
                 7.00E−06 
                 88 
                 194.2 
                 0.45 
               
               
                   
                   
                 like (yeast) 
               
               
                 209199_s_at 
                 MEF2C 
                 MADS box transcription enhancer 
                 7.00E−06 
                 561.9 
                 79.6 
                 7.06 
               
               
                   
                   
                 factor 2, polypeptide C (myocyte 
               
               
                   
                   
                 enhancer factor 2C) 
               
               
                 216218_s_at 
                 PLCL2 
                 phospholipase C-like 2 
                 7.00E−06 
                 34 
                 10.8 
                 3.15 
               
               
                 227419_x_at 
                 PLAC9 
                 placenta-specific 9 
                 7.00E−06 
                 179.3 
                 58.5 
                 3.06 
               
               
                 213603_s_at 
                 RAC2 
                 ras-related C3 botulinum toxin 
                 8.00E−06 
                 1278.7 
                 247.4 
                 5.17 
               
               
                   
                   
                 substrate 2 (rho family, small GTP 
               
               
                   
                   
                 binding protein Rac2) 
               
               
                 209447_at 
                 SYNE1 
                 spectrin repeat containing, nuclear 
                 8.00E−06 
                 171.8 
                 38.9 
                 4.42 
               
               
                   
                   
                 envelope 1 
               
               
                 219452_at 
                 DPEP2 
                 dipeptidase 2 
                 8.00E−06 
                 49.7 
                 22.2 
                 2.24 
               
               
                 232676_x_at 
                 MYEF2 
                 myelin expression factor 2 
                 8.00E−06 
                 82.2 
                 228.8 
                 0.36 
               
               
                 200807_s_at 
                 HSPD1 
                 heat shock 60 kDa protein 1 
                 8.00E−06 
                 2153.1 
                 4492.3 
                 0.48 
               
               
                   
                   
                 (chaperonin) 
               
               
                 219183_s_at 
                 PSCD4 
                 pleckstrin homology, Sec7 and 
                 8.00E−06 
                 152.8 
                 67.1 
                 2.28 
               
               
                   
                   
                 coiled-coil domains 4 
               
               
                 236517_at 
                 MEGF10 
                 multiple EGF-like-domains 10 
                 9.00E−06 
                 30.3 
                 8.4 
                 3.61 
               
               
                 224451_x_at 
                 ARHGAP9 
                 Rho GTPase activating protein 9 
                 9.00E−06 
                 270.3 
                 65.5 
                 4.13 
               
               
                 218708_at 
                 NXT1 
                 NTF2-like export factor 1 
                 9.00E−06 
                 121.4 
                 253.2 
                 0.48 
               
               
                 211135_x_at 
                 LILRB2/ 
                 leukocyte immunoglobulin-like 
                 9.00E−06 
                 185.8 
                 109.8 
                 1.69 
               
               
                   
                 LILRB3 
                 receptor, subfamily B (with TM and 
               
               
                   
                   
                 ITIM domains), member 2/leukocyte 
               
               
                   
                   
                 immunoglobulin-like receptor, 
               
               
                   
                   
                 subfamily B (with TM and ITIM 
               
               
                   
                   
                 domains), member 3 
               
               
                 224929_at 
                 LOC340061 
                 hypothetical protein LOC340061 
                 1.00E−05 
                 182.1 
                 74.3 
                 2.45 
               
               
                 204628_s_at 
                 ITGB3 
                 integrin, beta 3 (platelet glycoprotein 
                 1.00E−05 
                 45.1 
                 24.7 
                 1.83 
               
               
                   
                   
                 IIIa, antigen CD61) 
               
               
                 230413_s_at 
                 AP1S2 
                 Adaptor-related protein complex 1, 
                 1.00E−05 
                 37.5 
                 15.2 
                 2.47 
               
               
                   
                   
                 sigma 2 subunit 
               
               
                 205644_s_at 
                 SNRPG 
                 small nuclear ribonucleoprotein 
                 1.00E−05 
                 1079.8 
                 2300.1 
                 0.47 
               
               
                   
                   
                 polypeptide G 
               
               
                 219947_at 
                 CLEC4A 
                 C-type lectin domain family 4, 
                 1.00E−05 
                 70.1 
                 19.8 
                 3.54 
               
               
                   
                   
                 member A 
               
               
                 1598_g_at 
                 GAS6 
                 growth arrest-specific 6 
                  1.1e−05 
                 625.7 
                 245.8 
                 2.55 
               
               
                 209716_at 
                 CSF1 
                 colony stimulating factor 1 
                  1.1e−05 
                 204.5 
                 110.6 
                 1.85 
               
               
                   
                   
                 (macrophage) 
               
               
                 219191_s_at 
                 BIN2 
                 bridging integrator 2 
                  1.1e−05 
                 237 
                 64.5 
                 3.67 
               
               
                 226673_at 
                 SH2D3C 
                 SH2 domain containing 3C 
                  1.1e−05 
                 87.7 
                 46.2 
                 1.90 
               
               
                 213715_s_at 
                 ANKRD47 
                 ankyrin repeat domain 47 
                  1.2e−05 
                 67.3 
                 39.4 
                 1.71 
               
               
                 222771_s_at 
                 MYEF2 
                 myelin expression factor 2 
                  1.1e−05 
                 27.2 
                 84.1 
                 0.32 
               
               
                 1552316_a_at 
                 GIMAP1 
                 GTPase, IMAP family member 1 
                  1.2e−05 
                 62.8 
                 18.5 
                 3.39 
               
               
                 220765_s_at 
                 LIMS2 
                 LIM and senescent cell antigen-like 
                  1.2e−05 
                 116 
                 71.7 
                 1.62 
               
               
                   
                   
                 domains 2 
               
               
                 230264_s_at 
                 AP1S2 
                 adaptor-related protein complex 1, 
                  1.2e−05 
                 761 
                 153.1 
                 4.97 
               
               
                   
                   
                 sigma 2 subunit 
               
               
                 208335_s_at 
                 DARC 
                 Duffy blood group, chemokine 
                  1.4e−05 
                 108.4 
                 30.2 
                 3.59 
               
               
                   
                   
                 receptor 
               
               
                 204852_s_at 
                 PTPN7 
                 protein tyrosine phosphatase, non- 
                  1.4e−05 
                 64.7 
                 27.1 
                 2.39 
               
               
                   
                   
                 receptor type 7 
               
               
                 202911_at 
                 MSH6 
                 mutS homolog 6 ( E. coli ) 
                  1.5e−05 
                 203.1 
                 370.6 
                 0.55 
               
               
                 228376_at 
                 GGTA1 
                 Glycoprotein, alpha- 
                  1.5e−05 
                 278.7 
                 72.8 
                 3.83 
               
               
                   
                   
                 galactosyltransferase 1 
               
               
                 235359_at 
                 LRRC33 
                 leucine rich repeat containing 33 
                  1.5e−05 
                 93.8 
                 33.1 
                 2.83 
               
               
                 32502_at 
                 GDPD5 
                 glycerophosphodiester 
                  1.5e−05 
                 140 
                 77.1 
                 1.82 
               
               
                   
                   
                 phosphodiesterase domain 
               
               
                   
                   
                 containing 5 
               
               
                 209002_s_at 
                 CALCOCO1 
                 calcium binding and coiled-coil 
                  1.5e−05 
                 191.5 
                 89.7 
                 2.13 
               
               
                   
                   
                 domain 1 
               
               
                 226863_at 
                 FAM110C 
                 Family with sequence similarity 110 
                  1.5e−05 
                 17.6 
                 183.1 
                 0.10 
               
               
                   
                   
                 member C 
               
               
                 228311_at 
                 BCL6B 
                 B-cell CLL/lymphoma 6, member B 
                  1.5e−05 
                 81.2 
                 49.9 
                 1.63 
               
               
                   
                   
                 (zinc finger protein) 
               
               
                 228339_at 
                 LOC641700 
                 Hypothetical protein LOC641700 
                  1.5e−05 
                 65.4 
                 34 
                 1.92 
               
               
                 1555811_at 
                 ARHGDIB 
                 Rho GDP dissociation inhibitor (GDI) 
                  1.5e−05 
                 141.8 
                 92.3 
                 1.54 
               
               
                   
                   
                 beta 
               
               
                 212793_at 
                 DAAM2 
                 dishevelled associated activator of 
                  1.5e−05 
                 146.1 
                 43 
                 3.40 
               
               
                   
                   
                 morphogenesis 2 
               
               
                 217549_at 
                   
                 Transcribed locus, strongly similar to 
                  1.5e−05 
                 90 
                 46.2 
                 1.95 
               
               
                   
                   
                 NP_848718.1 mitochondrial 
               
               
                   
                   
                 ribosomal protein L50 [ Mus   
               
               
                   
                   
                   musculus ] 
               
               
                 209354_at 
                 TNFRSF14 
                 tumor necrosis factor receptor 
                  1.6e−05 
                 138.9 
                 81.1 
                 1.71 
               
               
                   
                   
                 superfamily, member 14 (herpesvirus 
               
               
                   
                   
                 entry mediator) 
               
               
                 215382_x_at 
                 TPSAB1 
                 tryptase alpha/beta 1 
                  1.6e−05 
                 143.1 
                 40 
                 3.58 
               
               
                 210340_s_at 
                 CSF2RA 
                 colony stimulating factor 2 receptor, 
                  1.7e−05 
                 27.6 
                 16.2 
                 1.70 
               
               
                   
                   
                 alpha, low-affinity (granulocyte- 
               
               
                   
                   
                 macrophage) 
               
               
                 225763_at 
                 RCSD1 
                 RCSD domain containing 1 
                  1.6e−05 
                 166.3 
                 36.3 
                 4.58 
               
               
                 228677_s_at 
                 FLJ21438 
                 hypothetical protein FLJ21438 
                  1.7e−05 
                 131.4 
                 75.5 
                 1.74 
               
               
                 244598_at 
                 LOC133874 
                 Hypothetical gene LOC133874 
                  1.7e−05 
                 37.1 
                 22.5 
                 1.65 
               
               
                 200696_s_at 
                 GSN 
                 gelsolin (amyloidosis, Finnish type) 
                  1.7e−05 
                 2017.7 
                 659.7 
                 3.06 
               
               
                 203813_s_at 
                 SLIT3 
                 slit homolog 3 ( Drosophila ) 
                  1.7e−05 
                 86.1 
                 35.5 
                 2.43 
               
               
                 216033_s_at 
                 FYN 
                 FYN oncogene related to SRC, FGR, 
                  1.7e−05 
                 83.1 
                 25.4 
                 3.27 
               
               
                   
                   
                 YES 
               
               
                 207677_s_at 
                 NCF4 
                 neutrophil cytosolic factor 4, 40 kDa 
                  1.7e−05 
                 96.2 
                 17 
                 5.66 
               
               
                 207238_s_at 
                 PTPRC 
                 protein tyrosine phosphatase, 
                  1.8e−05 
                 448.9 
                 75.6 
                 5.94 
               
               
                   
                   
                 receptor type, C 
               
               
                 211742_s_at 
                 EVI2B 
                 ecotropic viral integration site 2B 
                  1.8e−05 
                 582.2 
                 93.5 
                 6.23 
               
               
                 212556_at 
                 SCRIB 
                 scribbled homolog ( Drosophila ) 
                  1.8e−05 
                 104.2 
                 305.5 
                 0.34 
               
               
                 228332_s_at 
                 C11orf31 
                 chromosome 11 open reading frame 
                  1.8e−05 
                 755.4 
                 1868.8 
                 0.40 
               
               
                   
                   
                 31 
               
               
                 237563_s_at 
                 LOC440731 
                 hypothetical LOC440731 
                  1.8e−05 
                 48.2 
                 202.7 
                 0.24 
               
               
                 203176_s_at 
                 TFAM 
                 transcription factor A, mitochondrial 
                  1.9e−05 
                 30.1 
                 68.8 
                 0.44 
               
               
                 220966_x_at 
                 ARPC5L 
                 actin related protein ⅔ complex, 
                  1.8e−05 
                 263.1 
                 475.4 
                 0.55 
               
               
                   
                   
                 subunit 5-like 
               
               
                 223562_at 
                 PARVG 
                 parvin, gamma 
                  1.9e−05 
                 139.6 
                 63.4 
                 2.20 
               
               
                 216041_x_at 
                 GRN 
                 granulin 
                 2.00E−05 
                 1187.5 
                 416 
                 2.85 
               
               
                 204249_s_at 
                 LMO2 
                 LIM domain only 2 (rhombotin-like 1) 
                  2.1e−05 
                 381.4 
                 96.7 
                 3.94 
               
               
                 51176_at 
                 CRSP8 
                 cofactor required for Sp1 
                 2.00E−05 
                 96.6 
                 181 
                 0.53 
               
               
                   
                   
                 transcriptional activation, subunit 8, 
               
               
                   
                   
                 34 kDa 
               
               
                 1557228_at 
                 EHBP1L1 
                 EH domain binding protein 1-like 1 
                  2.1e−05 
                 112.4 
                 68.2 
                 1.65 
               
               
                 218460_at 
                 HEATR2 
                 HEAT repeat containing 2 
                  2.1e−05 
                 182.5 
                 366.4 
                 0.50 
               
               
                 205147_x_at 
                 NCF4 
                 neutrophil cytosolic factor 4, 40 kDa 
                  2.1e−05 
                 87 
                 23.2 
                 3.75 
               
               
                 228424_at 
                 NAALADL1 
                 N-acetylated alpha-linked acidic 
                  2.1e−05 
                 70.9 
                 42 
                 1.69 
               
               
                   
                   
                 dipeptidase-like 1 
               
               
                 200678_x_at 
                 GRN 
                 granulin 
                  2.2e−05 
                 1213.4 
                 436.3 
                 2.78 
               
               
                 203331_s_at 
                 INPP5D 
                 inositol polyphosphate-5- 
                  2.2e−05 
                 34.5 
                 17.6 
                 1.96 
               
               
                   
                   
                 phosphatase, 145 kDa 
               
               
                 207339_s_at 
                 LTB 
                 lymphotoxin beta (TNF superfamily, 
                  2.2e−05 
                 126.8 
                 68.6 
                 1.85 
               
               
                   
                   
                 member 3) 
               
               
                 233252_s_at 
                 STRBP 
                 spermatid perinuclear RNA binding 
                  2.2e−05 
                 33.5 
                 100.9 
                 0.33 
               
               
                   
                   
                 protein 
               
               
                 45749_at 
                 FAM65A 
                 family with sequence similarity 65, 
                  2.2e−05 
                 458.7 
                 298.3 
                 1.54 
               
               
                   
                   
                 member A 
               
               
                 203865_s_at 
                 ADARB1 
                 adenosine deaminase, RNA-specific, 
                  2.2e−05 
                 151 
                 43.3 
                 3.49 
               
               
                   
                   
                 B1 (RED1 homolog rat) 
               
               
                 218999_at 
                 TMEM140 
                 transmembrane protein 140 
                  2.3e−05 
                 208.3 
                 86.5 
                 2.41 
               
               
                 221080_s_at 
                 DENND1C 
                 DENN/MADD domain containing 1C 
                  2.3e−05 
                 111.6 
                 64 
                 1.74 
               
               
                 203103_s_at 
                 PRPF19 
                 PRP19/PSO4 pre-mRNA processing 
                  2.3e−05 
                 209.6 
                 392.9 
                 0.53 
               
               
                   
                   
                 factor 19 homolog ( S. cerevisiae ) 
               
               
                 203332_s_at 
                 INPP5D 
                 inositol polyphosphate-5- 
                  2.3e−05 
                 165.2 
                 69.6 
                 2.37 
               
               
                   
                   
                 phosphatase, 145 kDa 
               
               
                 205467_at 
                 CASP10 
                 caspase 10, apoptosis-related 
                  2.3e−05 
                 65.2 
                 39.8 
                 1.64 
               
               
                   
                   
                 cysteine peptidase 
               
               
                 227371_at 
                 BAIAP2L1 
                 BAI1-associated protein 2-like 1 
                  2.4e−05 
                 28 
                 83.7 
                 0.33 
               
               
                 238638_at 
                 SLC37A2 
                 solute carrier family 37 (glycerol-3- 
                  2.3e−05 
                 66.1 
                 30.9 
                 2.14 
               
               
                   
                   
                 phosphate transporter), member 2 
               
               
                 238905_at 
                 RHOJ 
                 ras homolog gene family, member J 
                  2.3e−05 
                 41.6 
                 27 
                 1.54 
               
               
                 212885_at 
                 MPHOSPH10 
                 M-phase phosphoprotein 10 (U3 
                  2.4e−05 
                 140.5 
                 230.1 
                 0.61 
               
               
                   
                   
                 small nucleolar ribonucleoprotein) 
               
               
                 204228_at 
                 PPIH 
                 peptidylprolyl isomerase H 
                  2.4e−05 
                 181.6 
                 360.7 
                 0.50 
               
               
                   
                   
                 (cyclophilin H) 
               
               
                 204346_s_at 
                 RASSF1 
                 Ras association (RalGDS/AF-6) 
                  2.4e−05 
                 70.8 
                 34.8 
                 2.03 
               
               
                   
                   
                 domain family 1 
               
               
                 211284_s_at 
                 GRN 
                 granulin 
                  2.4e−05 
                 813.4 
                 316.6 
                 2.57 
               
               
                 217948_at 
                   
                   
                  2.4e−05 
                 83.7 
                 158.2 
                 0.53 
               
               
                 223640_at 
                 HCST 
                 hematopoietic cell signal transducer 
                  2.5e−05 
                 204.1 
                 74.1 
                 2.75 
               
               
                 1559584_a_at 
                 C16orf54 
                 chromosome 16 open reading frame 
                  2.5e−05 
                 31.6 
                 8.5 
                 3.72 
               
               
                   
                   
                 54 
               
               
                 211781_x_at 
                   
                   
                  2.5e−05 
                 43.3 
                 28.2 
                 1.54 
               
               
                 220161_s_at 
                 EPB41L4B 
                 erythrocyte membrane protein band 
                  2.5e−05 
                 51 
                 306.5 
                 0.17 
               
               
                   
                   
                 4.1 like 4B 
               
               
                 35974_at 
                 LRMP 
                 lymphoid-restricted membrane 
                  2.5e−05 
                 39 
                 17.2 
                 2.27 
               
               
                   
                   
                 protein 
               
               
                 201721_s_at 
                 LAPTM5 
                 lysosomal associated multispanning 
                  2.6e−05 
                 1823.2 
                 278.4 
                 6.55 
               
               
                   
                   
                 membrane protein 5 
               
               
                 205277_at 
                 PRDM2 
                 PR domain containing 2, with ZNF 
                  2.6e−05 
                 48.4 
                 28.5 
                 1.70 
               
               
                   
                   
                 domain 
               
               
                 226632_at 
                 CYGB 
                 cytoglobin 
                  2.6e−05 
                 126.8 
                 34.6 
                 3.66 
               
               
                 226996_at 
                 LYCAT 
                 lysocardiolipin acyltransferase 
                  2.6e−05 
                 120.3 
                 288.5 
                 0.42 
               
               
                 204638_at 
                 ACP5 
                 acid phosphatase 5, tartrate resistant 
                  2.7e−05 
                 695.6 
                 131.7 
                 5.28 
               
               
                 210659_at 
                 CMKLR1 
                 chemokine-like receptor 1 
                  2.8e−05 
                 29.4 
                 18.8 
                 1.56 
               
               
                 1294_at 
                 UBE1L 
                 ubiquitin-activating enzyme E1-like 
                  2.8e−05 
                 142.5 
                 76.4 
                 1.87 
               
               
                 203668_at 
                 MAN2C1 
                 mannosidase, alpha, class 2C, 
                  2.8e−05 
                 53 
                 27.8 
                 1.91 
               
               
                   
                   
                 member 1 
               
               
                 205611_at 
                 TNFSF12 
                 tumor necrosis factor (ligand) 
                  2.8e−05 
                 81.7 
                 45.2 
                 1.81 
               
               
                   
                   
                 superfamily, member 12 
               
               
                 215380_s_at 
                 C7orf24 
                 chromosome 7 open reading frame 
                  2.8e−05 
                 450.4 
                 1424.9 
                 0.32 
               
               
                   
                   
                 24 
               
               
                 227520_at 
                 Cxorf15 
                 chromosome X open reading frame 
                  2.8e−05 
                 63.2 
                 184.2 
                 0.34 
               
               
                   
                   
                 15 
               
               
                 228899_at 
                 CUL1 
                 Cullin 1 
                  2.9e−05 
                 37.6 
                 132.4 
                 0.28 
               
               
                 204790_at 
                 SMAD7 
                 SMAD, mothers against DPP 
                  2.9e−05 
                 212.7 
                 61.6 
                 3.45 
               
               
                   
                   
                 homolog 7 ( Drosophila ) 
               
               
                 205718_at 
                 ITGB7 
                 integrin, beta 7 
                 3.00E−05 
                 105.4 
                 65 
                 1.62 
               
               
                 221087_s_at 
                 APOL3 
                 apolipoprotein L, 3 
                 3.00E−05 
                 126 
                 58.4 
                 2.16 
               
               
                 201121_s_at 
                 PGRMC1 
                 progesterone receptor membrane 
                  3.1e−05 
                 540.9 
                 1149.9 
                 0.47 
               
               
                   
                   
                 component 1 
               
               
                 217848_s_at 
                 PPA1 
                 pyrophosphatase (inorganic) 1 
                  3.1e−05 
                 1169.5 
                 2990.1 
                 0.39 
               
               
                 202933_s_at 
                 YES1 
                 v-yes-1 Yamaguchi sarcoma viral 
                  3.2e−05 
                 139.8 
                 508.3 
                 0.28 
               
               
                   
                   
                 oncogene homolog 1 
               
               
                 202995_s_at 
                 FBLN1 
                 fibulin 1 
                  3.2e−05 
                 271.4 
                 35.7 
                 7.60 
               
               
                 209280_at 
                 MRC2 
                 mannose receptor, C type 2 
                  3.2e−05 
                 209.1 
                 109 
                 1.92 
               
               
                 202009_at 
                 PTK9L 
                 PTK9L protein tyrosine kinase 9-like 
                  3.3e−05 
                 110.5 
                 63 
                 1.75 
               
               
                   
                   
                 (A6-related protein) 
               
               
                 200785_s_at 
                 LRP1 
                 low density lipoprotein-related protein 
                  3.4e−05 
                 191.5 
                 80.1 
                 2.39 
               
               
                   
                   
                 1 (alpha-2-macroglobulin receptor) 
               
               
                 203426_s_at 
                 IGFBP5 
                 insulin-like growth factor binding 
                  3.4e−05 
                 57.9 
                 31.5 
                 1.84 
               
               
                   
                   
                 protein 5 
               
               
                 207134_x_at 
                 TPSAB1 
                 tryptase alpha/beta 1 
                  3.4e−05 
                 189.6 
                 36.9 
                 5.14 
               
               
                 218882_s_at 
                 WDR3 
                 WD repeat domain 3 
                  3.4e−05 
                 81.8 
                 208 
                 0.39 
               
               
                 218239_s_at 
                 GTPBP4 
                 GTP binding protein 4 
                  3.5e−05 
                 148.7 
                 367.8 
                 0.40 
               
               
                 203425_s_at 
                 IGFBP5 
                 insulin-like growth factor binding 
                  3.6e−05 
                 78.7 
                 38 
                 2.07 
               
               
                   
                   
                 protein 5 
               
               
                 205312_at 
                 SPI1 
                 spleen focus forming virus (SFFV) 
                  3.6e−05 
                 63.2 
                 24 
                 2.63 
               
               
                   
                   
                 proviral integration oncogene spi1 
               
               
                 209879_at 
                 SELPLG 
                 selectin P ligand 
                  3.6e−05 
                 139 
                 55.7 
                 2.50 
               
               
                 1554503_a_at 
                 OSCAR 
                 osteoclast-associated receptor 
                  3.7e−05 
                 26.5 
                 13.5 
                 1.96 
               
               
                 210044_s_at 
                 LYL1 
                 lymphoblastic □aematolo derived 
                  3.6e−05 
                 105.3 
                 38.1 
                 2.76 
               
               
                   
                   
                 sequence 1 
               
               
                 238673_at 
                   
                 Transcribed locus 
                  3.8e−05 
                 18.5 
                 122.6 
                 0.15 
               
               
                 209302_at 
                 POLR2H 
                 polymerase (RNA) II (DNA directed) 
                  3.8e−05 
                 267.8 
                 626.8 
                 0.43 
               
               
                   
                   
                 polypeptide H 
               
               
                 212426_s_at 
                 YWHAQ 
                 tyrosine 3- 
                  3.9e−05 
                 858.9 
                 1978.5 
                 0.43 
               
               
                   
                   
                 monooxygenase/tryptophan 5- 
               
               
                   
                   
                 monooxygenase activation protein, 
               
               
                   
                   
                 theta polypeptide 
               
               
                 212766_s_at 
                 ISG20L2 
                 interferon stimulated exonuclease 
                  3.9e−05 
                 90 
                 354 
                 0.25 
               
               
                   
                   
                 gene 20 kDa-like 2 
               
               
                 227821_at 
                 LGI4 
                 leucine-rich repeat LGI family, 
                  3.9e−05 
                 136.9 
                 72.4 
                 1.89 
               
               
                   
                   
                 member 4 
               
               
                 201991_s_at 
                 KIF5B 
                 kinesin family member 5B 
                 4.00E−05 
                 759.2 
                 1298.7 
                 0.58 
               
               
                 216474_x_at 
                 TPSAB1 
                 tryptase alpha/beta 1 
                 4.00E−05 
                 280.2 
                 54.6 
                 5.13 
               
               
                 228541_x_at 
                 NGRN 
                 Neugrin, neurite outgrowth 
                 4.00E−05 
                 150.8 
                 307.7 
                 0.49 
               
               
                   
                   
                 associated 
               
               
                 204122_at 
                 TYROBP 
                 TYRO protein tyrosine kinase binding 
                  4.2e−05 
                 1090.6 
                 210.6 
                 5.18 
               
               
                   
                   
                 protein 
               
               
                 220751_s_at 
                 C5orf4 
                 chromosome 5 open reading frame 4 
                  4.1e−05 
                 207.5 
                 61.9 
                 3.35 
               
               
                 201597_at 
                 COX7A2 
                 cytochrome c oxidase subunit VIIa 
                  4.2e−05 
                 1215.4 
                 2497.4 
                 0.49 
               
               
                   
                   
                 polypeptide 2 (liver) 
               
               
                 203186_s_at 
                 S100A4 
                 S100 calcium binding protein A4 
                  4.2e−05 
                 1747.6 
                 256.4 
                 6.82 
               
               
                   
                   
                 (calcium protein, calvasculin, 
               
               
                   
                   
                 metastasin, murine placental 
               
               
                   
                   
                 homolog) 
               
               
                 206267_s_at 
                 MATK 
                 megakaryocyte-associated tyrosine 
                  4.2e−05 
                 90.1 
                 45.7 
                 1.97 
               
               
                   
                   
                 kinase 
               
               
                 218465_at 
                 TMEM33 
                 transmembrane protein 33 
                  4.2e−05 
                 79.5 
                 203.2 
                 0.39 
               
               
                 223553_s_at 
                 DOK3 
                 docking protein 3 
                  4.2e−05 
                 164.7 
                 41.3 
                 3.99 
               
               
                 229295_at 
                 LOC150166 
                 hypothetical protein LOC150166 
                  4.3e−05 
                 191.3 
                 75.7 
                 2.53 
               
               
                 228519_x_at 
                 CIRBP 
                 cold inducible RNA binding protein 
                  4.4e−05 
                 148.9 
                 75.9 
                 1.96 
               
               
                 234299_s_at 
                 NIN 
                 ninein (GSK3B interacting protein) 
                  4.3e−05 
                 25.5 
                 15.5 
                 1.65 
               
               
                 213381_at 
                 C10orf72 
                 Chromosome 10 open reading frame 
                  4.4e−05 
                 48.5 
                 30.3 
                 1.60 
               
               
                   
                   
                 72 
               
               
                 204789_at 
                 FMNL1 
                 formin-like 1 
                  4.5e−05 
                 101.1 
                 54.2 
                 1.87 
               
               
                 236029_at 
                 FAT3 
                 FAT tumor suppressor homolog 3 
                  4.5e−05 
                 64 
                 10.8 
                 5.93 
               
               
                   
                   
                 ( Drosophila ) 
               
               
                 204193_at 
                 CHKB/ 
                 choline kinase beta/carnitine 
                  4.7e−05 
                 263.2 
                 141.2 
                 1.86 
               
               
                   
                 CPT1B 
                 palmitoyltransferase 1B (muscle) 
               
               
                 206055_s_at 
                 SNRPA1 
                 small nuclear ribonucleoprotein 
                  4.6e−05 
                 208.5 
                 536.2 
                 0.39 
               
               
                   
                   
                 polypeptide A′ 
               
               
                 219243_at 
                 GIMAP4 
                 GTPase, IMAP family member 4 
                  4.7e−05 
                 323.9 
                 130 
                 2.49 
               
               
                 221827_at 
                 C20orf18 
                 chromosome 20 open reading frame 
                  4.7e−05 
                 137.9 
                 357.2 
                 0.39 
               
               
                   
                   
                 18 
               
               
                 223690_at 
                 LTBP2 
                 latent transforming growth factor beta 
                  4.6e−05 
                 559.4 
                 155.4 
                 3.60 
               
               
                   
                   
                 binding protein 2 
               
               
                 228410_at 
                 GAB3 
                 GRB2-associated binding protein 3 
                  4.6e−05 
                 83.5 
                 36.5 
                 2.29 
               
               
                 201468_s_at 
                 NQO1 
                 NAD(P)H dehydrogenase, quinone 1 
                  4.8e−05 
                 160.5 
                 737.6 
                 0.22 
               
               
                 210075_at 
                 MARCH2 
                 membrane-associated ring finger 
                  4.7e−05 
                 113.2 
                 49.2 
                 2.30 
               
               
                   
                   
                 (C3HC4) 2 
               
               
                 213733_at 
                 MYO1F 
                 myosin IF 
                  4.7e−05 
                 223.2 
                 63.3 
                 3.53 
               
               
                 205709_s_at 
                 CDS1 
                 CDP-diacylglycerol synthase 
                  4.9e−05 
                 60.5 
                 302.8 
                 0.20 
               
               
                   
                   
                 (phosphatidate cytidylyltransferase) 1 
               
               
                 211056_s_at 
                 SRD5A1 
                 steroid-5-alpha-reductase, alpha 
                  4.8e−05 
                 50.3 
                 127.6 
                 0.39 
               
               
                   
                   
                 polypeptide 1 (3-oxo-5 alpha-steroid 
               
               
                   
                   
                 delta 4-dehydrogenase alpha 1) 
               
               
                 231991_at 
                 C20orf160 
                 chromosome 20 open reading frame 
                  4.8e−05 
                 53.2 
                 30 
                 1.77 
               
               
                   
                   
                 160 
               
               
                 234306_s_at 
                 SLAMF7 
                 SLAM family member 7 
                  4.9e−05 
                 27.8 
                 16.7 
                 1.66 
               
               
                 202666_s_at 
                 ACTL6A 
                 actin-like 6A 
                 5.00E−05 
                 132.3 
                 425 
                 0.31 
               
               
                 236583_at 
                 ABP1 
                 Amiloride binding protein 1 (amine 
                 5.00E−05 
                 45.7 
                 26 
                 1.76 
               
               
                   
                   
                 oxidase (copper-containing)) 
               
               
                 201558_at 
                 RAE1 
                 RAE1 RNA export 1 homolog ( S. Pombe ) 
                  5.1e−05 
                 251.1 
                 607.1 
                 0.41 
               
               
                 209348_s_at 
                 MAF 
                 v-maf musculoaponeurotic 
                  5.2e−05 
                 499.3 
                 150.5 
                 3.32 
               
               
                   
                   
                 fibrosarcoma oncogene homolog 
               
               
                   
                   
                 (avian) 
               
               
                 219689_at 
                 SEMA3G 
                 sema domain, immunoglobulin 
                  5.2e−05 
                 148.3 
                 53.2 
                 2.79 
               
               
                   
                   
                 domain (Ig), short basic domain, 
               
               
                   
                   
                 secreted, (□aematologi) 3G 
               
               
                 220005_at 
                 P2RY13 
                 purinergic receptor P2Y, G-protein 
                  5.2e−05 
                 62.6 
                 14.7 
                 4.26 
               
               
                   
                   
                 coupled, 13 
               
               
                 241227_at 
                   
                   
                  5.2e−05 
                 55.1 
                 34.5 
                 1.60 
               
               
                 218606_at 
                 ZDHHC7 
                 zinc finger, DHHC-type containing 7 
                  5.3e−05 
                 480.4 
                 317.8 
                 1.51 
               
               
                 213541_s_at 
                 ERG 
                 v-ets erythroblastosis virus E26 
                  5.4e−05 
                 51.9 
                 21.2 
                 2.45 
               
               
                   
                   
                 oncogene like (avian) 
               
               
                 227779_at 
                 LOC641700 
                 Hypothetical protein LOC641700 
                  5.4e−05 
                 30.2 
                 18.4 
                 1.64 
               
               
                 201540_at 
                 FHL1 
                 four and a half LIM domains 1 
                  5.6e−05 
                 1551.7 
                 177.8 
                 8.73 
               
               
                 206682_at 
                 CLEC10A 
                 C-type lectin domain family 10, 
                  5.8e−05 
                 50.7 
                 28.3 
                 1.79 
               
               
                   
                   
                 member A 
               
               
                 53968_at 
                 INTS5 
                 integrator complex subunit 5 
                  5.7e−05 
                 66.4 
                 159.2 
                 0.42 
               
               
                 59375_at 
                 MYO15B 
                 myosin XVB pseudogene 
                  5.8e−05 
                 75.5 
                 40.6 
                 1.86 
               
               
                 214450_at 
                 CTSW 
                 cathepsin W (lymphopain) 
                  5.8e−05 
                 86.9 
                 42.6 
                 2.04 
               
               
                 222218_s_at 
                 PILRA 
                 paired immunoglobin-like type 2 
                  5.8e−05 
                 111.9 
                 43.1 
                 2.60 
               
               
                   
                   
                 receptor alpha 
               
               
                 222396_at 
                 HN1 
                 □aematological and neurological 
                  5.8e−05 
                 116.5 
                 268.9 
                 0.43 
               
               
                   
                   
                 expressed 1 
               
               
                 235849_at 
                 SCARA5 
                 scavenger receptor class A, member 
                  5.9e−05 
                 147.6 
                 48.4 
                 3.05 
               
               
                   
                   
                 5 (putative) 
               
               
                 241742_at 
                 PRAM1 
                 PML-RARA regulated adaptor 
                  5.9e−05 
                 68.4 
                 23.7 
                 2.89 
               
               
                   
                   
                 molecule 1 
               
               
                 202735_at 
                 EBP 
                 emopamil binding protein (sterol 
                 6.00E−05 
                 143.9 
                 238.8 
                 0.60 
               
               
                   
                   
                 isomerase) 
               
               
                 207697_x_at 
                 LILRB2 
                 leukocyte immunoglobulin-like 
                  6.1e−05 
                 107.8 
                 45.7 
                 2.36 
               
               
                   
                   
                 receptor, subfamily B (with TM and 
               
               
                   
                   
                 ITIM domains), member 2 
               
               
                 210569_s_at 
                 SIGLEC9 
                 sialic acid binding Ig-like lectin 9 
                  5.9e−05 
                 28.9 
                 18.7 
                 1.55 
               
               
                 227159_at 
                 LGP1 
                 homolog of mouse LGP1 
                  5.9e−05 
                 82.3 
                 50.2 
                 1.64 
               
               
                 209549_s_at 
                 DGUOK 
                 deoxyguanosine kinase 
                  6.2e−05 
                 260.4 
                 466.9 
                 0.56 
               
               
                 214005_at 
                 GGCX 
                 gamma-glutamyl carboxylase 
                  6.2e−05 
                 56.6 
                 160.8 
                 0.35 
               
               
                 235907_at 
                   
                 Transcribed locus 
                  6.1e−05 
                 39.6 
                 117.9 
                 0.34 
               
               
                 203281_s_at 
                 UBE1L 
                 ubiquitin-activating enzyme E1-like 
                  6.4e−05 
                 181.1 
                 80.4 
                 2.25 
               
               
                 222742_s_at 
                 RABL5 
                 RAB, member RAS oncogene family- 
                  6.4e−05 
                 187.5 
                 404.5 
                 0.46 
               
               
                   
                   
                 like 5 
               
               
                 229941_at 
                   
                   
                  6.4e−05 
                 43.1 
                 26.6 
                 1.62 
               
               
                 205883_at 
                 ZBTB16 
                 zinc finger and BTB domain 
                  6.6e−05 
                 42.3 
                 18.2 
                 2.32 
               
               
                   
                   
                 containing 16 
               
               
                 210084_x_at 
                 TPSAB1 
                 tryptase alpha/beta 1 
                  6.6e−05 
                 177.3 
                 41.8 
                 4.24 
               
               
                 223096_at 
                 NOP5/NOP58 
                 nucleolar protein NOP5/NOP58 
                  6.6e−05 
                 528.3 
                 1218.9 
                 0.43 
               
               
                 200953_s_at 
                 CCND2 
                 cyclin D2 
                  6.8e−05 
                 175.6 
                 50 
                 3.51 
               
               
                 209582_s_at 
                 CD200 
                 CD200 molecule 
                  6.8e−05 
                 31.2 
                 13.2 
                 2.36 
               
               
                 232164_s_at 
                 EPPK1 
                 epiplakin 1 
                  6.7e−05 
                 30 
                 294.4 
                 0.10 
               
               
                 220320_at 
                 DOK3 
                 docking protein 3 
                 7.00E−05 
                 47.2 
                 26.2 
                 1.80 
               
               
                 1558828_s_at 
                 DKFZp586C0721 
                 Hypothetical protein 
                 7.00E−05 
                 51.5 
                 21.4 
                 2.41 
               
               
                   
                   
                 DKFZp586C0721 
               
               
                 201326_at 
                 CCT6A 
                 chaperonin containing TCP1, subunit 
                  7.1e−05 
                 255.7 
                 537.7 
                 0.48 
               
               
                   
                   
                 6A (zeta 1) 
               
               
                 228139_at 
                 RIPK3 
                 receptor-interacting serine-threonine 
                  7.1e−05 
                 51.6 
                 28.7 
                 1.80 
               
               
                   
                   
                 kinase 3 
               
               
                 38149_at 
                 ARHGAP25 
                 Rho GTPase activating protein 25 
                  7.1e−05 
                 110 
                 42.9 
                 2.56 
               
               
                 201040_at 
                 GNAI2 
                 guanine nucleotide binding protein (G 
                  7.2e−05 
                 291.3 
                 150.2 
                 1.94 
               
               
                   
                   
                 protein), alpha inhibiting activity 
               
               
                   
                   
                 polypeptide 2 
               
               
                 211800_s_at 
                 USP4 
                 ubiquitin specific peptidase 4 (proto- 
                  7.2e−05 
                 208.6 
                 107.8 
                 1.94 
               
               
                   
                   
                 oncogene) 
               
               
                 222056_s_at 
                 FAHD2A 
                 fumarylacetoacetate hydrolase 
                  7.3e−05 
                 77.8 
                 164.4 
                 0.47 
               
               
                   
                   
                 domain containing 2A 
               
               
                 225381_at 
                 LOC399959 
                 hypothetical gene supported by 
                  7.2e−05 
                 65.4 
                 16.2 
                 4.04 
               
               
                   
                   
                 BX647608 
               
               
                 229491_at 
                 LOC133308 
                 hypothetical protein BC009732 
                  7.2e−05 
                 104.7 
                 30.2 
                 3.47 
               
               
                 237324_s_at 
                 HKDC1 
                 hexokinase domain containing 1 
                  7.2e−05 
                 26 
                 16.3 
                 1.60 
               
               
                 202877_s_at 
                 CD93 
                 CD93 molecule 
                  7.4e−05 
                 124.3 
                 50.5 
                 2.46 
               
               
                 225543_at 
                 GTF3C4 
                 General transcription factor IIIC, 
                  7.5e−05 
                 44.5 
                 107.1 
                 0.42 
               
               
                   
                   
                 polypeptide 4, 90 kDa 
               
               
                 229041_s_at 
                 ITGB2 
                 Integrin, beta 2 (complement 
                  7.5e−05 
                 90.3 
                 31.5 
                 2.87 
               
               
                   
                   
                 component 3 receptor 3 and 4 
               
               
                   
                   
                 subunit) 
               
               
                 204256_at 
                 ELOVL6 
                 ELOVL family member 6, elongation 
                  7.6e−05 
                 28.4 
                 87.8 
                 0.32 
               
               
                   
                   
                 of long chain fatty acids (FEN1/Elo2, 
               
               
                   
                   
                 SUR4/Elo3-like, yeast) 
               
               
                 209651_at 
                 TGFB1I1 
                 transforming growth factor beta 1 
                  7.6e−05 
                 160.9 
                 59.9 
                 2.69 
               
               
                   
                   
                 induced transcript 1 
               
               
                 229121_at 
                   
                 CDNA FLJ44441 fis, clone 
                  7.7e−05 
                 85.7 
                 39.7 
                 2.16 
               
               
                   
                   
                 UTERU2020242 
               
               
                 200058_s_at 
                 ASCC3L1 
                 activating signal cointegrator 1 
                  7.8e−05 
                 548.2 
                 989.7 
                 0.55 
               
               
                   
                   
                 complex subunit 3-like 1 
               
               
                 205418_at 
                 FES 
                 feline sarcoma oncogene 
                  7.9e−05 
                 69.8 
                 38.3 
                 1.82 
               
               
                 207741_x_at 
                 TPSAB1/ 
                 tryptase alpha/beta 1/tryptase beta 2 
                  7.7e−05 
                 131.2 
                 43.6 
                 3.01 
               
               
                   
                 TPSB2 
               
               
                 209948_at 
                 KCNMB1 
                 potassium large conductance 
                  7.8e−05 
                 76 
                 36.4 
                 2.09 
               
               
                   
                   
                 calcium-activated channel, subfamily 
               
               
                   
                   
                 M, beta member 1 
               
               
                 218434_s_at 
                 AACS 
                 acetoacetyl-CoA synthetase 
                  7.8e−05 
                 93.1 
                 225 
                 0.41 
               
               
                 1553155_x_at 
                 ATP6V0D2 
                 ATPase, H+ transporting, lysosomal 
                 8.00E−05 
                 32.5 
                 16.5 
                 1.97 
               
               
                   
                   
                 38 kDa, V0 subunit d2 
               
               
                 213309_at 
                 PLCL2 
                 phospholipase C-like 2 
                 8.00E−05 
                 90.2 
                 32 
                 2.82 
               
               
                 212281_s_at 
                 TMEM97 
                 transmembrane protein 97 
                  8.2e−05 
                 55 
                 292.1 
                 0.19 
               
               
                 219347_at 
                 NUDT15 
                 nudix (nucleoside diphosphate linked 
                  8.1e−05 
                 27.9 
                 90.6 
                 0.31 
               
               
                   
                   
                 moiety X)-type motif 15 
               
               
                 242402_x_at 
                   
                   
                  8.2e−05 
                 59.5 
                 38.8 
                 1.53 
               
               
                 201089_at 
                 ATP6V1B2 
                 ATPase, H+ transporting, lysosomal 
                  8.4e−05 
                 629.6 
                 191.4 
                 3.29 
               
               
                   
                   
                 56/58 kDa, V1 subunit B2 
               
               
                 203119_at 
                 CCDC86 
                 coiled-coil domain containing 86 
                  8.6e−05 
                 71.1 
                 127.4 
                 0.56 
               
               
                 217249_x_at 
                   
                   
                  8.5e−05 
                 252.2 
                 511.7 
                 0.49 
               
               
                 228477_at 
                 FLJ10154 
                 Hypothetical protein FLJ10154 
                  8.5e−05 
                 395.2 
                 219.3 
                 1.80 
               
               
                 227557_at 
                 SCARF2 
                 scavenger receptor class F, member 2 
                  8.8e−05 
                 59.1 
                 35.8 
                 1.65 
               
               
                 203300_x_at 
                 AP1S2 
                 adaptor-related protein complex 1, 
                 9.00E−05 
                 408.4 
                 108.7 
                 3.76 
               
               
                   
                   
                 sigma 2 subunit 
               
               
                 209583_s_at 
                 CD200 
                 CD200 molecule 
                  8.9e−05 
                 178.5 
                 57.9 
                 3.08 
               
               
                 226187_at 
                 CDS1 
                 CDP-diacylglycerol synthase 
                 9.00E−05 
                 41.6 
                 141.5 
                 0.29 
               
               
                   
                   
                 (phosphatidate cytidylyltransferase) 1 
               
               
                 204223_at 
                 PRELP 
                 proline/arginine-rich end leucine-rich 
                  9.2e−05 
                 336.1 
                 92.1 
                 3.65 
               
               
                   
                   
                 repeat protein 
               
               
                 205377_s_at 
                 ACHE 
                 acetylcholinesterase (Yt blood group) 
                  9.1e−05 
                 36.9 
                 17.2 
                 2.15 
               
               
                 210299_s_at 
                 FHL1 
                 four and a half LIM domains 1 
                  9.2e−05 
                 476.2 
                 34.6 
                 13.76 
               
               
                 235306_at 
                 GIMAP8 
                 GTPase, IMAP family member 8 
                  9.2e−05 
                 113.6 
                 32.1 
                 3.54 
               
               
                 212390_at 
                 PDE4DIP 
                 phosphodiesterase 4D interacting 
                  9.4e−05 
                 480.5 
                 69.5 
                 6.91 
               
               
                   
                   
                 protein (myomegalin) 
               
               
                 213915_at 
                 NKG7 
                 natural killer cell group 7 sequence 
                  9.5e−05 
                 94.6 
                 24.5 
                 3.86 
               
               
                 225372_at 
                 C10orf54 
                 chromosome 10 open reading frame 
                  9.3e−05 
                 39.4 
                 20.8 
                 1.89 
               
               
                   
                   
                 54 
               
               
                 232922_s_at 
                 C20orf59 
                 chromosome 20 open reading frame 
                  9.3e−05 
                 55.1 
                 33.9 
                 1.63 
               
               
                   
                   
                 59 
               
               
                 203175_at 
                 RHOG 
                 ras homolog gene family, member G 
                  9.7e−05 
                 385.2 
                 181.5 
                 2.12 
               
               
                   
                   
                 (rho G) 
               
               
                 219282_s_at 
                 TRPV2 
                 transient receptor potential cation 
                  9.6e−05 
                 92 
                 35.8 
                 2.57 
               
               
                   
                   
                 channel, subfamily V, member 2 
               
               
                 222010_at 
                 TCP1 
                 t-complex 1 
                  9.7 e −05 
                 67.9 
                 166.8 
                 0.41 
               
               
                 227156_at 
                 TNRC8 
                 trinucleotide repeat containing 8 
                  9.7e−05 
                 30.5 
                 117.2 
                 0.26 
               
               
                 221246_x_at 
                 TNS1 
                 tensin 1 
                  9.9e−05 
                 253.4 
                 138.5 
                 1.83 
               
               
                 224677_x_at 
                 C11orf31 
                 chromosome 11 open reading frame 
                  9.9e−05 
                 452.7 
                 742.4 
                 0.61 
               
               
                   
                   
                 31 
               
               
                   
               
            
           
           
               
            
               
                 LUNG METASTASIS ASSOCIATED MARKERS 
               
            
           
           
               
               
               
            
               
                   
                 Geometric mean of 
                   
               
               
                   
                 intensities in 
                 ratio 
               
            
           
           
               
               
               
               
               
               
            
               
                   
                 Gene 
                   
                 Parametric p- 
                 Lung 
                 Non_Lung 
               
               
                 Probe Set 
                 Symbol 
                 Gene Title 
                 value 
                 metastases 
                 metastases 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                 204751_x_at 
                 DSC2 
                 desmocollin 2 
                 p &lt; 0.000001 
                 249.1 
                 30.4 
                 8.19 
               
               
                 235651_at 
                   
                   
                 p &lt; 0.000001 
                 158.3 
                 16.4 
                 9.65 
               
               
                 223861_at 
                 HORMAD1 
                 HORMA domain containing 1 
                 2.00E−06 
                 219.7 
                 10.2 
                 21.54 
               
               
                 228171_s_at 
                 PLEKHG4 
                 pleckstrin homology domain 
                 2.00E−06 
                 109.5 
                 40.5 
                 2.70 
               
               
                   
                   
                 containing, family G (with RhoGef 
               
               
                   
                   
                 domain) member 4 
               
               
                 228577_x_at 
                 ODF2L 
                 outer dense fiber of sperm tails 2-like 
                 8.00E−06 
                 44.3 
                 15.3 
                 2.90 
               
               
                 220941_s_at 
                 C21orf91 
                 chromosome 21 open reading frame 
                 1.00E−05 
                 96.2 
                 26.7 
                 3.60 
               
               
                   
                   
                 91 
               
               
                 227642_at 
                 TFCP2L1 
                 Transcription factor CP2-like 1 
                 1.00E−05 
                 278.2 
                 50.6 
                 5.50 
               
               
                 229523_at 
                 TTMA 
                 Two transmembrane domain family 
                 1.30E−05 
                 73.6 
                 20.1 
                 3.66 
               
               
                   
                   
                 member A 
               
               
                 219867_at 
                 CHODL 
                 chondrolectin 
                 1.40E−05 
                 49.2 
                 17.3 
                 2.84 
               
               
                 205428_s_at 
                 CALB2 
                 calbindin 2, 29 kDa (calretinin) 
                 1.60E−05 
                 327.4 
                 35.6 
                 9.20 
               
               
                 228956_at 
                 UGT8 
                 UDP glycosyltransferase 8 (UDP- 
                 1.80E−05 
                 191.1 
                 12.4 
                 15.41 
               
               
                   
                   
                 galactose ceramide 
               
               
                   
                   
                 galactosyltransferase) 
               
               
                 227452_at 
                 LOC146795 
                 Hypothetical protein LOC146795 
                 1.80E−05 
                 139.4 
                 25.8 
                 5.40 
               
               
                 1554246_at 
                 C1orf210 
                 chromosome 1 open reading frame 
                 2.10E−05 
                 45.4 
                 19.9 
                 2.28 
               
               
                   
                   
                 210 
               
               
                 221705_s_at 
                 SIKE 
                 suppressor of IKK epsilon 
                 2.10E−05 
                 30.6 
                 16.5 
                 1.85 
               
               
                 211488_s_at 
                 ITGB8 
                 integrin, beta 8 
                 2.60E−05 
                 25.5 
                 14.7 
                 1.73 
               
               
                 213372_at 
                 PAQR3 
                 progestin and adipoQ receptor family 
                 2.90E−05 
                 322.5 
                 57.2 
                 5.64 
               
               
                   
                   
                 member III 
               
               
                 208103_s_at 
                 ANP32E 
                 acidic (leucine-rich) nuclear 
                 3.20E−05 
                 333.7 
                 55.7 
                 5.99 
               
               
                   
                   
                 phosphoprotein 32 family, member E 
               
               
                 60474_at 
                 KIND1 
                 chromosome 20 open reading frame 
                 3.60E−05 
                 113.3 
                 16.5 
                 6.87 
               
               
                   
                   
                 42 
               
               
                 222869_s_at 
                 ELAC1 
                 elaC homolog 1 ( E. coli ) 
                 3.60E−05 
                 38 
                 23.3 
                 1.63 
               
               
                 227829_at 
                 GYLTL1B 
                 glycosyltransferase-like 1B 
                 3.90E−05 
                 187.1 
                 70.9 
                 2.64 
               
               
                 231033_at 
                   
                 Full length insert cDNA clone 
                 3.90E−05 
                 71.9 
                 16.6 
                 4.33 
               
               
                   
                   
                 YI40A07 
               
               
                 226075_at 
                 SPSB1 
                 splA/ryanodine receptor domain and 
                 5.60E−05 
                 92.3 
                 31.9 
                 2.89 
               
               
                   
                   
                 SOCS box containing 1 
               
               
                 214596_at 
                 CHRM3 
                 cholinergic receptor, muscarinic 3 
                 6.10E−05 
                 38 
                 18.8 
                 2.02 
               
               
                 225363_at 
                 PTEN 
                 Phosphatase and tensin homolog 
                 6.20E−05 
                 235.3 
                 569.9 
                 0.41 
               
               
                   
                   
                 (mutated in multiple advanced 
               
               
                   
                   
                 cancers 1) 
               
               
                 242488_at 
                   
                 CDNA FLJ38396 fis, clone 
                 6.20E−05 
                 60.2 
                 19 
                 3.17 
               
               
                   
                   
                 FEBRA2007957 
               
               
                 213889_at 
                 PIGL 
                 phosphatidylinositol glycan, class L 
                 6.60E−05 
                 37.9 
                 21.2 
                 1.79 
               
               
                 1553705_a_at 
                 CHRM3 
                 cholinergic receptor, muscarinic 3 
                 7.00E−05 
                 30.8 
                 16.7 
                 1.84 
               
               
                 203256_at 
                 CDH3 
                 cadherin 3, type 1, P-cadherin 
                 9.50E−05 
                 252.2 
                 41.4 
                 6.09 
               
               
                   
                   
                 (placental) 
               
               
                   
               
            
           
           
               
            
               
                 LIVER METASTASIS ASSOCIATED MARKERS 
               
            
           
           
               
               
               
            
               
                   
                 Geometric mean of 
                   
               
               
                   
                 intensities in 
                 ratio 
               
            
           
           
               
               
               
               
               
               
            
               
                   
                 Gene 
                   
                 Parametric p- 
                 Liver 
                 Non_Liver 
               
               
                 Probe Set 
                 Symbol 
                 Gene Title 
                 value 
                 metastases 
                 metastases 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                 239847_at 
                   
                 CDNA clone IMAGE: 6186815 
                 p &lt; 0.000001 
                 107 
                 24.7 
                 4.33 
               
               
                 219682_s_at 
                 TBX3 
                 T-box 3 (ulnar mammary syndrome) 
                 p &lt; 0.000001 
                 515.5 
                 45.4 
                 11.35 
               
               
                 225544_at 
                 TBX3 
                 T-box 3 (ulnar mammary syndrome) 
                 p &lt; 0.000001 
                 345.6 
                 57.2 
                 6.04 
               
               
                 229053_at 
                 SYT17 
                 Synaptotagmin XVII 
                 p &lt; 0.000001 
                 142.6 
                 17.9 
                 7.97 
               
               
                 221823_at 
                 LOC90355 
                 hypothetical gene supported by 
                 p &lt; 0.000001 
                 420.5 
                 91.6 
                 4.59 
               
               
                   
                   
                 AF038182; BC009203 
               
               
                 221008_s_at 
                 AGXT2L1 
                 alanine-glyoxylate aminotransferase 
                 0.000001 
                 30.6 
                 8.3 
                 3.69 
               
               
                   
                   
                 2-like 1 
               
               
                 1557415_s_at 
                 LETM2 
                 leucine zipper-EF-hand containing 
                 0.000001 
                 27.1 
                 14.5 
                 1.87 
               
               
                   
                   
                 transmembrane protein 2 
               
               
                 1558881_at 
                 LOC145820 
                 hypothetical protein LOC145820 
                 0.000001 
                 25.7 
                 14.6 
                 1.76 
               
               
                 228718_at 
                 ZNF44 
                 zinc finger protein 44 
                 0.000002 
                 48.9 
                 16.7 
                 2.93 
               
               
                 219115_s_at 
                 IL20RA 
                 interleukin 20 receptor, alpha 
                 0.000002 
                 63 
                 15.8 
                 3.99 
               
               
                 226344_at 
                 ZMAT1 
                 zinc finger, matrin type 1 
                 0.000003 
                 144 
                 36.6 
                 3.93 
               
               
                 214156_at 
                 MYRIP 
                 myosin VIIA and Rab interacting 
                 0.000003 
                 37 
                 12 
                 3.08 
               
               
                   
                   
                 protein 
               
               
                 218173_s_at 
                 WHSC1L1 
                 Wolf-Hirschhorn syndrome candidate 
                 0.000003 
                 80.5 
                 21.5 
                 3.74 
               
               
                   
                   
                 1-like 1 
               
               
                 225561_at 
                 SELT 
                 selenoprotein T 
                 0.000003 
                 436.3 
                 107.6 
                 4.05 
               
               
                 238496_at 
                 WHSC1L1 
                 Wolf-Hirschhorn syndrome candidate 
                 0.000003 
                 135.3 
                 37.6 
                 3.60 
               
               
                   
                   
                 1-like 1 
               
               
                 209710_at 
                 GATA2 
                 GATA binding protein 2 
                 0.000003 
                 367.9 
                 80.5 
                 4.57 
               
               
                 239638_at 
                   
                 CDNA FLJ33227 fis, clone 
                 0.000004 
                 44 
                 17.6 
                 2.50 
               
               
                   
                   
                 ASTRO2001088 
               
               
                 207988_s_at 
                 ARPC2 
                 actin related protein ⅔ complex, 
                 0.000005 
                 600 
                 1062.5 
                 0.56 
               
               
                   
                   
                 subunit 2, 34 kDa 
               
               
                 225915_at 
                 CAB39L 
                 calcium binding protein 39-like 
                 0.000006 
                 130.3 
                 23.3 
                 5.59 
               
               
                 217691_x_at 
                 SLC16A3 
                 solute carrier family 16 
                 0.000006 
                 66.9 
                 145.6 
                 0.46 
               
               
                   
                   
                 (monocarboxylic acid transporters), 
               
               
                   
                   
                 member 3 
               
               
                 235675_at 
                 DHFRL1 
                 dihydrofolate reductase-like 1 
                 0.000007 
                 76.5 
                 18.9 
                 4.05 
               
               
                 229908_s_at 
                   
                 CDNA: FLJ21189 fis, clone 
                 0.000007 
                 142.6 
                 77.9 
                 1.83 
               
               
                   
                   
                 CAS11887 
               
               
                 1556308_at 
                 PRRT3 
                 proline-rich transmembrane protein 3 
                 0.000007 
                 173.4 
                 44.7 
                 3.88 
               
               
                 242981_at 
                 CYP3A5 
                 Cytochrome P450, family 3, 
                 0.000007 
                 57 
                 29 
                 1.97 
               
               
                   
                   
                 subfamily A, polypeptide 5 
               
               
                 204635_at 
                 RPS6KA5 
                 ribosomal protein S6 kinase, 90 kDa, 
                 0.000008 
                 145 
                 52.7 
                 2.75 
               
               
                   
                   
                 polypeptide 5 
               
               
                 227091_at 
                 KIAA1505 
                 KIAA1505 protein 
                 0.000008 
                 91.8 
                 36.7 
                 2.50 
               
               
                 239859_x_at 
                 ATP5S 
                 ATP synthase, H+ transporting, 
                 0.000008 
                 42.4 
                 24.5 
                 1.73 
               
               
                   
                   
                 mitochondrial F0 complex, subunit s 
               
               
                   
                   
                 (factor B) 
               
               
                 1555982_at 
                 ZFYVE16 
                 Zinc finger, FYVE domain containing 
                 0.000009 
                 77.4 
                 19.5 
                 3.97 
               
               
                   
                   
                 16 
               
               
                 213118_at 
                 KIAA0701 
                 KIAA0701 protein 
                 0.000009 
                 165.6 
                 59.4 
                 2.79 
               
               
                 230570_at 
                   
                 Transcribed locus 
                 0.000009 
                 95.4 
                 22.8 
                 4.18 
               
               
                 236117_at 
                   
                 Transcribed locus 
                 0.000009 
                 49.6 
                 19.5 
                 2.54 
               
               
                 237083_at 
                   
                 Transcribed locus 
                 0.000009 
                 26.6 
                 11.3 
                 2.35 
               
               
                 210825_s_at 
                 PEBP1 
                 phosphatidylethanolamine binding 
                 0.00001 
                 4026.3 
                 1903.1 
                 2.12 
               
               
                   
                   
                 protein 1 
               
               
                 238719_at 
                   
                 Transcribed locus 
                 0.00001 
                 92.6 
                 48.8 
                 1.90 
               
               
                 225318_at 
                 DDHD2 
                 DDHD domain containing 2 
                 0.000012 
                 489.1 
                 139.8 
                 3.50 
               
               
                 212637_s_at 
                 WWP1 
                 WW domain containing E3 ubiquitin 
                 0.000012 
                 291.8 
                 45 
                 6.48 
               
               
                   
                   
                 protein ligase 1 
               
               
                 229602_at 
                   
                 Transcribed locus 
                 0.000013 
                 45.3 
                 21.1 
                 2.15 
               
               
                 222312_s_at 
                   
                 CDNA clone IMAGE: 6186815 
                 0.000014 
                 143.7 
                 53.3 
                 2.70 
               
               
                 1555827_at 
                 CCNL1 
                 Cyclin L1 
                 0.000014 
                 33 
                 15.7 
                 2.10 
               
               
                 226766_at 
                 ROBO2 
                 roundabout, axon guidance receptor, 
                 0.000015 
                 27.8 
                 10.1 
                 2.75 
               
               
                   
                   
                 homolog 2 ( Drosophila ) 
               
               
                 244749_at 
                 FAM111B 
                 Family with sequence similarity 111, 
                 0.000015 
                 34.5 
                 13.3 
                 2.59 
               
               
                   
                   
                 member B 
               
               
                 212209_at 
                 THRAP2 
                 thyroid hormone receptor associated 
                 0.000017 
                 391.1 
                 157.1 
                 2.49 
               
               
                   
                   
                 protein 2 
               
               
                 204349_at 
                 CRSP9 
                 cofactor required for Sp1 
                 0.000017 
                 119.4 
                 61.5 
                 1.94 
               
               
                   
                   
                 transcriptional activation, subunit 9, 
               
               
                   
                   
                 33 kDa 
               
               
                 217191_x_at 
                   
                   
                 0.000019 
                 50.4 
                 23.6 
                 2.14 
               
               
                 227582_at 
                 KARCA1 
                 kelch/ankyrin repeat containing cyclin 
                 0.00002 
                 305.1 
                 81.6 
                 3.74 
               
               
                   
                   
                 A1 interacting protein 
               
               
                 231069_at 
                   
                 Transcribed locus 
                 0.00002 
                 76 
                 18.3 
                 4.15 
               
               
                 202856_s_at 
                 SLC16A3 
                 solute carrier family 16 
                 0.000021 
                 39.1 
                 244.6 
                 0.16 
               
               
                   
                   
                 (monocarboxylic acid transporters), 
               
               
                   
                   
                 member 3 
               
               
                 224076_s_at 
                 WHSC1L1 
                 Wolf-Hirschhorn syndrome candidate 
                 0.000022 
                 293.1 
                 84.4 
                 3.47 
               
               
                   
                   
                 1-like 1 
               
               
                 230141_at 
                 ARID4A 
                 AT rich interactive domain 4A (RBP1- 
                 0.000024 
                 59.2 
                 25.3 
                 2.34 
               
               
                   
                   
                 like) 
               
               
                 204045_at 
                 TCEAL1 
                 transcription elongation factor A (SII)- 
                 0.000025 
                 638.9 
                 179.6 
                 3.56 
               
               
                   
                   
                 like 1 
               
               
                 212425_at 
                 SCAMP1 
                 Secretory carrier membrane protein 1 
                 0.000025 
                 72.9 
                 31.5 
                 2.31 
               
               
                 242366_at 
                 KIAA0701 
                 KIAA0701 protein 
                 0.000025 
                 127.8 
                 52.6 
                 2.43 
               
               
                 213757_at 
                 EIF5A 
                 Eukaryotic translation initiation factor 
                 0.000027 
                 194.8 
                 467.4 
                 0.42 
               
               
                   
                   
                 5A 
               
               
                 228039_at 
                 DDX46G 
                 DEAD (Asp-Glu-Ala-Asp) box 
                 0.000027 
                 205.3 
                 82.2 
                 2.50 
               
               
                   
                   
                 polypeptide 46 
               
               
                 205420_at 
                 PEX7 
                 peroxisomal biogenesis factor 7 
                 0.000031 
                 101.9 
                 34.3 
                 2.97 
               
               
                 204633_s_at 
                 RPS6KA5 
                 ribosomal protein S6 kinase, 90 kDa, 
                 0.000032 
                 252.3 
                 88.5 
                 2.85 
               
               
                   
                   
                 polypeptide 5 
               
               
                 225606_at 
                 BCL2L11 
                 BCL2-like 11 (apoptosis facilitator) 
                 0.000032 
                 399.4 
                 187.5 
                 2.13 
               
               
                 208628_s_at 
                 YBX1 
                 Y box binding protein 1 
                 0.000033 
                 849.7 
                 2307.6 
                 0.37 
               
               
                 239437_at 
                   
                 Transcribed locus 
                 0.000033 
                 66.6 
                 22.6 
                 2.95 
               
               
                 208760_at 
                 UBE2I 
                 Ubiquitin-conjugating enzyme E2I 
                 0.000034 
                 275.1 
                 97.5 
                 2.82 
               
               
                   
                   
                 (UBC9 homolog, yeast) 
               
               
                 223989_s_at 
                 REXO2 
                 REX2, RNA exonuclease 2 homolog 
                 0.000034 
                 60.4 
                 95 
                 0.64 
               
               
                   
                   
                 ( S. cerevisiae ) 
               
               
                 225557_at 
                 AXUD1 
                 AXIN1 up-regulated 1 
                 0.000035 
                 159.4 
                 74 
                 2.15 
               
               
                 1563189_at 
                   
                 CDNA: FLJ20907 fis, clone 
                 0.000036 
                 38.4 
                 17.5 
                 2.19 
               
               
                   
                   
                 ADSE00408 
               
               
                 223126_s_at 
                 C1orf21 
                 chromosome 1 open reading frame 
                 0.000036 
                 226.4 
                 63 
                 3.59 
               
               
                   
                   
                 21 
               
               
                 1553719_s_at 
                 ZNF548 
                 zinc finger protein 548 
                 0.000037 
                 45.9 
                 17.7 
                 2.59 
               
               
                 227641_at 
                 FBXL16 
                 F-box and leucine-rich repeat protein 
                 0.000038 
                 524.3 
                 92.9 
                 5.64 
               
               
                   
                   
                 16 
               
               
                 1558345_a_at 
                 LOC439911 
                 hypothetical gene supported by 
                 0.000039 
                 93.4 
                 32.3 
                 2.89 
               
               
                   
                   
                 NM_194304 
               
               
                 1563629_a_at 
                 LOC283874 
                 hypothetical protein LOC283874 
                 0.000041 
                 72.7 
                 34.5 
                 2.11 
               
               
                 231820_x_at 
                 ZNF587 
                 zinc finger protein 587 
                 0.000041 
                 57.2 
                 22.5 
                 2.54 
               
               
                 218692_at 
                 FLJ20366 
                 hypothetical protein FLJ20366 
                 0.000042 
                 407.2 
                 59.3 
                 6.87 
               
               
                 235048_at 
                 KIAA0888 
                 KIAA0888 protein 
                 0.000044 
                 99.8 
                 24.9 
                 4.01 
               
               
                 1555848_at 
                   
                 MRNA full length insert cDNA clone 
                 0.000045 
                 87.2 
                 50.6 
                 1.72 
               
               
                   
                   
                 EUROIMAGE 1652049 
               
               
                 228189_at 
                 BAG4 
                 BCL2-associated athanogene 4 
                 0.000046 
                 648.4 
                 138.6 
                 4.68 
               
               
                 200757_s_at 
                 CALU 
                 calumenin 
                 0.000049 
                 264.5 
                 444.8 
                 0.59 
               
               
                 228768_at 
                 KIAA1961 
                 KIAA1961 gene 
                 0.000052 
                 312.1 
                 142.2 
                 2.19 
               
               
                 227572_at 
                 USP30 
                 Ubiquitin specific peptidase 30 
                 0.000054 
                 237.6 
                 115.1 
                 2.06 
               
               
                 237086_at 
                   
                   
                 0.000055 
                 168.6 
                 18.9 
                 8.92 
               
               
                 204622_x_at 
                 NR4A2 
                 nuclear receptor subfamily 4, group 
                 0.000056 
                 192.4 
                 38.1 
                 5.05 
               
               
                   
                   
                 A, member 2 
               
               
                 204667_at 
                 FOXA1 
                 forkhead box A1 
                 0.000055 
                 431.6 
                 41.9 
                 10.30 
               
               
                 231472_at 
                 FBXO15 
                 F-box protein 15 
                 0.000055 
                 79.2 
                 31.6 
                 2.51 
               
               
                 229158_at 
                 WNK4 
                 WNK lysine deficient protein kinase 4 
                 0.00006 
                 80.1 
                 22.8 
                 3.51 
               
               
                 1558279_a_at 
                   
                 CDNA FLJ36555 fis, clone 
                 0.000061 
                 27.7 
                 12.2 
                 2.27 
               
               
                   
                   
                 TRACH2008716 
               
               
                 201253_s_at 
                 CDIPT 
                 CDP-diacylglycerol--inositol 3- 
                 0.000061 
                 1517.7 
                 776.4 
                 1.95 
               
               
                   
                   
                 phosphatidyltransferase 
               
               
                   
                   
                 (phosphatidylinositol synthase) 
               
               
                 214053_at 
                   
                 Clone 23736 mRNA sequence 
                 0.000061 
                 198.4 
                 26 
                 7.63 
               
               
                 228328_at 
                   
                 CDNA FLJ33653 fis, clone 
                 0.000061 
                 138 
                 53.4 
                 2.58 
               
               
                   
                   
                 BRAMY2024715 
               
               
                 224477_s_at 
                 NUDT16L1 
                 nudix (nucleoside diphosphate linked 
                 0.000063 
                 144.7 
                 73.2 
                 1.98 
               
               
                   
                   
                 moiety X)-type motif 16-like 1 
               
               
                 225223_at 
                 SMAD5 
                 SMAD, mothers against DPP 
                 0.000063 
                 276.3 
                 103.4 
                 2.67 
               
               
                   
                   
                 homolog 5 ( Drosophila ) 
               
               
                 237706_at 
                 STXBP4 
                 Syntaxin binding protein 4 
                 0.000063 
                 27.1 
                 10.8 
                 2.51 
               
               
                 1556666_a_at 
                 TTC6 
                 tetratricopeptide repeat domain 6 
                 0.000064 
                 50.3 
                 10.5 
                 4.79 
               
               
                 242140_at 
                 LOC113386 
                 similar to envelope protein 
                 0.000066 
                 350.7 
                 73.2 
                 4.79 
               
               
                 1556665_at 
                 TTC6 
                 tetratricopeptide repeat domain 6 
                 0.000068 
                 44.3 
                 17.5 
                 2.53 
               
               
                 1560648_s_at 
                 TSPYL1 
                 TSPY-like 1 
                 0.000068 
                 27.5 
                 12.5 
                 2.20 
               
               
                 229069_at 
                 CIP29 
                 cytokine induced protein 29 kDa 
                 0.000069 
                 81 
                 43 
                 1.88 
               
               
                 204024_at 
                 C8orf1 
                 chromosome 8 open reading frame 1 
                 0.000071 
                 54.1 
                 19 
                 2.85 
               
               
                 221248_s_at 
                 WHSC1L1 
                 Wolf-Hirschhorn syndrome candidate 
                 0.000073 
                 30.4 
                 17.3 
                 1.76 
               
               
                   
                   
                 1-like 1 
               
               
                 227332_at 
                   
                 Full-length cDNA clone 
                 0.000074 
                 52.8 
                 24.8 
                 2.13 
               
               
                   
                   
                 CS0DD005YE10 of Neuroblastoma 
               
               
                   
                   
                 Cot 50-normalized of  Homo sapiens   
               
               
                   
                   
                 (human) 
               
               
                 238005_s_at 
                   
                 Transcribed locus 
                 0.000074 
                 115.6 
                 49 
                 2.36 
               
               
                 242245_at 
                 SYDE2 
                 Synapse defective 1, Rho GTPase, 
                 0.000075 
                 133.2 
                 22.2 
                 6.00 
               
               
                   
                   
                 homolog 2 ( C. elegans ) 
               
               
                 239024_at 
                 SLC12A8 
                 Solute carrier family 12 
                 0.000077 
                 68.2 
                 27.3 
                 2.50 
               
               
                   
                   
                 (potassium/chloride transporters), 
               
               
                   
                   
                 member 8 
               
               
                 223605_at 
                 SLC25A18 
                 solute carrier family 25 (mitochondrial 
                 0.000079 
                 39.7 
                 17 
                 2.34 
               
               
                   
                   
                 carrier), member 18 
               
               
                 229167_at 
                   
                 Full-length cDNA clone 
                 0.000079 
                 94.8 
                 51.2 
                 1.85 
               
               
                   
                   
                 CS0DF014YA22 of Fetal brain of 
               
               
                   
                   
                   Homo sapiens  (human) 
               
               
                 202992_at 
                 C7 
                 complement component 7 
                 0.000086 
                 365.4 
                 46.7 
                 7.82 
               
               
                 204226_at 
                 STAU2 
                 staufen, RNA binding protein, 
                 0.000085 
                 404.1 
                 110.7 
                 3.65 
               
               
                   
                   
                 homolog 2 ( Drosophila ) 
               
               
                 240557_at 
                 TSC22D2 
                 TSC22 domain family, member 2 
                 0.000086 
                 40.7 
                 19.8 
                 2.06 
               
               
                 204121_at 
                 GADD45G 
                 growth arrest and DNA-damage- 
                 0.000087 
                 81.3 
                 37.1 
                 2.19 
               
               
                   
                   
                 inducible, gamma 
               
               
                 217954_s_at 
                 PHF3 
                 PHD finger protein 3 
                 0.000087 
                 476.1 
                 251 
                 1.90 
               
               
                 239329_at 
                   
                 Transcribed locus 
                 0.000088 
                 78.3 
                 35.3 
                 2.22 
               
               
                 222820_at 
                 TNRC6C 
                 trinucleotide repeat containing 6C 
                 0.000089 
                 219.1 
                 54.3 
                 4.03 
               
               
                 227279_at 
                 TCEAL3 
                 transcription elongation factor A (SII)- 
                 0.000089 
                 848.7 
                 306.3 
                 2.77 
               
               
                   
                   
                 like 3 
               
               
                 242139_s_at 
                 LOC113386 
                 similar to envelope protein 
                 0.000092 
                 366.7 
                 98.8 
                 3.71 
               
               
                 222204_s_at 
                 RRN3 
                 RRN3 RNA polymerase I 
                 0.000097 
                 340.4 
                 125.2 
                 2.72 
               
               
                   
                   
                 transcription factor homolog ( S. cerevisiae ) 
               
               
                 224876_at 
                 C5orf24 
                 chromosome 5 open reading frame 
                 0.000097 
                 870.5 
                 444.3 
                 1.96 
               
               
                   
                   
                 24 
               
               
                 226115_at 
                 AHCTF1 
                 AT hook containing transcription 
                 0.000097 
                 218 
                 81.1 
                 2.69 
               
               
                   
                   
                 factor 1 
               
               
                 233198_at 
                 LOC92497 
                 hypothetical protein LOC92497 
                 0.000099 
                 159.4 
                 57.4 
                 2.78 
               
               
                   
               
            
           
           
               
            
               
                 BRAIN METASTASIS ASSOCIATED MARKERS 
               
            
           
           
               
               
               
            
               
                   
                 Geometric mean of 
                   
               
               
                   
                 intensities in 
                 ratio 
               
            
           
           
               
               
               
               
               
               
            
               
                   
                 Gene 
                   
                 Parametric p- 
                 Brain 
                 Non_Brain 
               
               
                 Probe Set 
                 Symbol 
                 Gene Title 
                 value 
                 Metastases 
                 Metastases 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                 1559822_s_at 
                 LOC644215 
                 Hypothetical protein LOC644215 
                 p &lt; 0.000001 
                 321.4 
                 111.7 
                 2.88 
               
               
                 212384_at 
                 BAT1 
                 HLA-B associated transcript 1 
                 p &lt; 0.000001 
                 37.5 
                 16.7 
                 2.25 
               
               
                 236946_at 
                 GPR75 
                 G protein-coupled receptor 75 
                 p &lt; 0.000001 
                 36.4 
                 19 
                 1.92 
               
               
                 213483_at 
                 PPWD1 
                 peptidylprolyl isomerase domain and 
                 p &lt; 0.000001 
                 34.8 
                 110.9 
                 0.31 
               
               
                   
                   
                 WD repeat containing 1 
               
               
                 217631_at 
                   
                   
                 p &lt; 0.000001 
                 29.6 
                 15.2 
                 1.95 
               
               
                 210141_s_at 
                 INHA 
                 inhibin, alpha 
                 p &lt; 0.000001 
                 27.1 
                 17.4 
                 1.56 
               
               
                 235596_at 
                   
                 Transcribed locus 
                 p &lt; 0.000001 
                 40.8 
                 23.3 
                 1.75 
               
               
                 203131_at 
                 PDGFRA 
                 platelet-derived growth factor 
                 p &lt; 0.000001 
                 23.1 
                 378.2 
                 0.06 
               
               
                   
                   
                 receptor, alpha polypeptide 
               
               
                 226100_at 
                 MLL5 
                 myeloid/lymphoid or mixed-lineage 
                 p &lt; 0.000001 
                 36.8 
                 110.5 
                 0.33 
               
               
                   
                   
                 leukemia 5 (trithorax homolog, 
               
               
                   
                   
                   Drosophila ) 
               
               
                 231457_at 
                   
                 Transcribed locus, strongly similar to 
                 1.00E−06 
                 53.4 
                 35 
                 1.53 
               
               
                   
                   
                 NP_116090.2 suppressor of 
               
               
                   
                   
                 variegation 4-20 homolog 2 [ Homo   
               
               
                   
                   
                   sapiens ] 
               
               
                 200926_at 
                 RPS23 
                 ribosomal protein S23 
                 1.00E−06 
                 5022.1 
                 8620.6 
                 0.58 
               
               
                 224694_at 
                 ANTXR1 
                 anthrax toxin receptor 1 
                 1.00E−06 
                 63.5 
                 464.8 
                 0.14 
               
               
                 235984_at 
                   
                   
                 2.00E−06 
                 71.9 
                 27.1 
                 2.65 
               
               
                 224797_at 
                 ARRDC3 
                 arrestin domain containing 3 
                 2.00E−06 
                 35.4 
                 205.6 
                 0.17 
               
               
                 239121_at 
                 PTK2 
                 PTK2 protein tyrosine kinase 2 
                 2.00E−06 
                 32.4 
                 20.1 
                 1.61 
               
               
                 244804_at 
                 SQSTM1 
                 Sequestosome 1 
                 3.00E−06 
                 98.1 
                 38.8 
                 2.53 
               
               
                 207761_s_at 
                 METTL7A 
                 methyltransferase like 7A 
                 3.00E−06 
                 149.8 
                 1011.8 
                 0.15 
               
               
                 223408_s_at 
                   
                   
                 4.00E−06 
                 56.2 
                 29.7 
                 1.89 
               
               
                 235410_at 
                 NPHP3 
                 nephronophthisis 3 (adolescent) 
                 4.00E−06 
                 28.5 
                 123 
                 0.23 
               
               
                 214154_s_at 
                 PKP2 
                 plakophilin 2 
                 4.00E−06 
                 38.2 
                 25.4 
                 1.50 
               
               
                 236210_at 
                 DDX31 
                 DEAD (Asp-Glu-Ala-Asp) box 
                 5.00E−06 
                 51.9 
                 23.6 
                 2.20 
               
               
                   
                   
                 polypeptide 31 
               
               
                 225572_at 
                 FAM119A 
                 Family with sequence similarity 119, 
                 5.00E−06 
                 80.4 
                 151 
                 0.53 
               
               
                   
                   
                 member A 
               
               
                 1558154_at 
                 LLGL2 
                 Lethal giant larvae homolog 2 
                 5.00E−06 
                 35.6 
                 18.4 
                 1.93 
               
               
                   
                   
                 ( Drosophila ) 
               
               
                 221780_s_at 
                 DDX27 
                 DEAD (Asp-Glu-Ala-Asp) box 
                 6.00E−06 
                 402.7 
                 159.8 
                 2.52 
               
               
                   
                   
                 polypeptide 27 
               
               
                 226839_at 
                 TRA16 
                 TR4 orphan receptor associated 
                 6.00E−06 
                 187.1 
                 78.4 
                 2.39 
               
               
                   
                   
                 protein TRA16 
               
               
                 209844_at 
                 HOXB13 
                 homeobox B13 
                 6.00E−06 
                 45.7 
                 25.2 
                 1.81 
               
               
                 229274_at 
                 GNAS 
                 GNAS complex locus 
                 6.00E−06 
                 34 
                 15.1 
                 2.25 
               
               
                 220072_at 
                 CSPP1 
                 centrosome and spindle pole 
                 7.00E−06 
                 40.1 
                 22.5 
                 1.78 
               
               
                   
                   
                 associated protein 1 
               
               
                 226237_at 
                 COLBA1 
                 Collagen, type VIII, alpha 1 
                 8.00E−06 
                 24.7 
                 368.2 
                 0.07 
               
               
                 220965_s_at 
                 RSHL1 
                 radial spokehead-like 1 
                 9.00E−06 
                 76.4 
                 46.7 
                 1.64 
               
               
                 213865_at 
                 DCBLD2 
                 discoidin, CUB and LCCL domain 
                 9.00E−06 
                 27.7 
                 14.6 
                 1.90 
               
               
                   
                   
                 containing 2 
               
               
                 212106_at 
                 UBXD8 
                 UBX domain containing 8 
                 9.00E−06 
                 175.9 
                 76.7 
                 2.29 
               
               
                 205224_at 
                 SURF2 
                 surfeit 2 
                 1.00E−05 
                 95.2 
                 55.7 
                 1.71 
               
               
                 225945_at 
                 ZNF655 
                 zinc finger protein 655 
                 1.00E−05 
                 54.6 
                 351.2 
                 0.16 
               
               
                 206103_at 
                 RAC3 
                 ras-related C3 botulinum toxin 
                 1.00E−05 
                 33 
                 17.5 
                 1.89 
               
               
                   
                   
                 substrate 3 (rho family, small GTP 
               
               
                   
                   
                 binding protein Rac3) 
               
               
                 209837_at 
                 AP4M1 
                 adaptor-related protein complex 4, 
                  1.1e−05 
                 36.4 
                 23.4 
                 1.56 
               
               
                   
                   
                 mu 1 subunit 
               
               
                 213069_at 
                 HEG1 
                 HEG homolog 1 (zebrafish) 
                  1.1e−05 
                 61.3 
                 273.5 
                 0.22 
               
               
                 229467_at 
                 PCBP2 
                 Poly(rC) binding protein 2 
                  1.1e−05 
                 149.8 
                 57.2 
                 2.62 
               
               
                 235432_at 
                 NPHP3 
                 nephronophthisis 3 (adolescent) 
                  1.2e−05 
                 13.5 
                 36.6 
                 0.37 
               
               
                 239596_at 
                 SLC30A7 
                 solute carrier family 30 (zinc 
                  1.3e−05 
                 34.1 
                 17.9 
                 1.91 
               
               
                   
                   
                 transporter), member 7 
               
               
                 233091_at 
                 ATAD3A/ 
                 ATPase family, AAA domain 
                  1.4e−05 
                 45.2 
                 29.5 
                 1.53 
               
               
                   
                 ATAD3B 
                 containing 3A/ATPase family, AAA 
               
               
                   
                   
                 domain containing 3B 
               
               
                 216546_s_at 
                 CHI3L1 
                 chitinase 3-like 1 (cartilage 
                  1.4e−05 
                 38.4 
                 24.8 
                 1.55 
               
               
                   
                   
                 glycoprotein-39) 
               
               
                 1565666_s_at 
                 MUC6 
                 mucin 6, oligomeric mucus/gel- 
                  1.5e−05 
                 107 
                 13.4 
                 7.99 
               
               
                   
                   
                 forming 
               
               
                 210719_s_at 
                 HMG20B 
                 high-mobility group 20B 
                  1.5e−05 
                 674 
                 127.9 
                 5.27 
               
               
                 203796_s_at 
                 BCL7A 
                 B-cell CLL/lymphoma 7A 
                  1.6e−05 
                 72.2 
                 35.6 
                 2.03 
               
               
                 244305_at 
                 GGN 
                 gametogenetin 
                  1.5e−05 
                 49.8 
                 30.1 
                 1.65 
               
               
                 241668_s_at 
                   
                   
                  1.6e−05 
                 30.8 
                 17.7 
                 1.74 
               
               
                 218501_at 
                 ARHGEF3 
                 Rho guanine nucleotide exchange 
                  1.7e−05 
                 75.8 
                 283.5 
                 0.27 
               
               
                   
                   
                 factor (GEF) 3 
               
               
                 200897_s_at 
                 PALLD 
                 palladin, cytoskeletal associated 
                  1.8e−05 
                 247.4 
                 998.9 
                 0.25 
               
               
                   
                   
                 protein 
               
               
                 208900_s_at 
                 TOP1 
                 topoisomerase (DNA) I 
                  1.8e−05 
                 104.4 
                 30.1 
                 3.47 
               
               
                 208823_s_at 
                 PCTK1 
                 PCTAIRE protein kinase 1 
                  1.9e−05 
                 192.7 
                 105.8 
                 1.82 
               
               
                 234654_at 
                 C20orf4 
                 Chromosome 20 open reading frame 4 
                 2.00E−05 
                 27.6 
                 17.5 
                 1.58 
               
               
                 213376_at 
                 ZBTB1 
                 zinc finger and BTB domain 
                 2.00E−05 
                 42.7 
                 143.4 
                 0.30 
               
               
                   
                   
                 containing 1 
               
               
                 229699_at 
                   
                 CDNA FLJ45384 fis, clone 
                  2.1e−05 
                 25.9 
                 75.5 
                 0.34 
               
               
                   
                   
                 BRHIP3021987 
               
               
                 240148_at 
                 MSH6 
                 MutS homolog 6 ( E. coli ) 
                 2.00E−05 
                 27.7 
                 16.5 
                 1.68 
               
               
                 239957_at 
                 SETD5 
                 SET domain containing 5 
                  2.1e−05 
                 45.6 
                 18.6 
                 2.45 
               
               
                 1555778_a_at 
                 POSTN 
                 periostin, osteoblast specific factor 
                  2.2e−05 
                 16.7 
                 495.4 
                 0.03 
               
               
                 206141_at 
                 MOCS3 
                 molybdenum cofactor synthesis 3 
                  2.1e−05 
                 71.4 
                 38 
                 1.88 
               
               
                 227428_at 
                 GABPA 
                 GA binding protein transcription 
                  2.2e−05 
                 21 
                 39.1 
                 0.54 
               
               
                   
                   
                 factor, alpha subunit 60 kDa 
               
               
                 223607_x_at 
                 ZSWIM1 
                 zinc finger, SWIM-type containing 1 
                  2.3e−05 
                 130 
                 82.9 
                 1.57 
               
               
                 219050_s_at 
                 ZNHIT2 
                 zinc finger, HIT type 2 
                  2.4e−05 
                 83.5 
                 50.5 
                 1.65 
               
               
                 236700_at 
                 LOC653352 
                 similar to eukaryotic translation 
                  2.3e−05 
                 28.5 
                 12.4 
                 2.30 
               
               
                   
                   
                 initiation factor 3, subunit 8 
               
               
                 204095_s_at 
                 ELL 
                 e elongation factor RNA 
                  2.4e−05 
                 67.9 
                 38.2 
                 1.78 
               
               
                   
                   
                 polymrase II 
               
               
                 217817_at 
                 ARPC4 
                 actin related protein ⅔ complex, 
                  2.4e−05 
                 650.6 
                 194 
                 3.35 
               
               
                   
                   
                 subunit 4, 20 kDa 
               
               
                 215887_at 
                 ZNF277 
                 zinc finger protein 277 
                  2.4e−05 
                 116.6 
                 61 
                 1.91 
               
               
                 205537_s_at 
                 VAV2 
                 vav 2 oncogene 
                  2.5e−05 
                 43.9 
                 27.5 
                 1.60 
               
               
                 210110_x_at 
                 HNRPH3 
                 heterogeneous nuclear 
                  2.6e−05 
                 68.1 
                 157.2 
                 0.43 
               
               
                   
                   
                 ribonucleoprotein H3 (2H9) 
               
               
                 206230_at 
                 LHX1 
                 LIM homeobox 1 
                  2.6e−05 
                 52.4 
                 25.8 
                 2.03 
               
               
                 238741_at 
                 FAM83A 
                 family with sequence similarity 83, 
                  2.9e−05 
                 85.3 
                 42.2 
                 2.02 
               
               
                   
                   
                 member A 
               
               
                 242970_at 
                 DIP2B 
                 DIP2 disco-interacting protein 2 
                  2.9e−05 
                 35.6 
                 19.9 
                 1.79 
               
               
                   
                   
                 homolog B ( Drosophila ) 
               
               
                 215089_s_at 
                 RBM10 
                 RNA binding motif protein 10 
                  3.1e−05 
                 284.5 
                 160.7 
                 1.77 
               
               
                 212088_at 
                 PMPCA 
                 peptidase (mitochondrial processing) 
                  3.1e−05 
                 221.1 
                 127.4 
                 1.74 
               
               
                   
                   
                 alpha 
               
               
                 225877_at 
                 TYSND1 
                 trypsin domain containing 1 
                  3.1e−05 
                 92.7 
                 37.4 
                 2.48 
               
               
                 237257_at 
                 RAB4B 
                 RAB4B, member RAS oncogene 
                  3.4e−05 
                 135.8 
                 77 
                 1.76 
               
               
                   
                   
                 family 
               
               
                 224822_at 
                 DLC1 
                 deleted in liver cancer 1 
                  3.4e−05 
                 46.7 
                 133 
                 0.35 
               
               
                 227433_at 
                 KIAA2018 
                 KIAA2018 
                  3.4e−05 
                 43 
                 146.6 
                 0.29 
               
               
                 244870_at 
                 TES 
                 testis derived transcript (3 LIM 
                  3.5e−05 
                 35 
                 22.8 
                 1.54 
               
               
                   
                   
                 domains) 
               
               
                 226157_at 
                 TFDP2 
                 Transcription factor Dp-2 (E2F 
                  3.7e−05 
                 40.5 
                 105.1 
                 0.39 
               
               
                   
                   
                 dimerization partner 2) 
               
               
                 224023_s_at 
                 C3orf10 
                 chromosome 3 open reading frame 
                  3.7e−05 
                 59.8 
                 31.7 
                 1.89 
               
               
                   
                   
                 10 
               
               
                 225512_at 
                 ZBTB38 
                 zinc finger and BTB domain 
                  3.9e−05 
                 62.9 
                 257.4 
                 0.24 
               
               
                   
                   
                 containing 38 
               
               
                 238738_at 
                 PSMD7 
                 Proteasome (prosome, macropain) 
                  3.9e−05 
                 49.9 
                 29.4 
                 1.70 
               
               
                   
                   
                 26S subunit, non-ATPase, 7 (Mov34 
               
               
                   
                   
                 homolog) 
               
               
                 205407_at 
                 RECK 
                 reversion-inducing-cysteine-rich 
                  4.1e−05 
                 10.6 
                 43.6 
                 0.24 
               
               
                   
                   
                 protein with kazal motifs 
               
               
                 221763_at 
                 JMJD1C 
                 jumonji domain containing 1C 
                  4.1e−05 
                 77.7 
                 234.7 
                 0.33 
               
               
                 229439_s_at 
                 FLJ20273 
                 RNA-binding protein 
                  4.1e−05 
                 111.6 
                 66.3 
                 1.68 
               
               
                 212437_at 
                 CENPB 
                 centromere protein B, 80 kDa 
                  4.3e−05 
                 203.4 
                 117.7 
                 1.73 
               
               
                 244374_at 
                 PLAC2 
                 placenta-specific 2 
                  4.3e−05 
                 59.1 
                 39.4 
                 1.50 
               
               
                 212179_at 
                 C6orf111 
                 chromosome 6 open reading frame 
                  4.4e−05 
                 92.3 
                 287.6 
                 0.32 
               
               
                   
                   
                 111 
               
               
                 213238_at 
                 ATP10D 
                 ATPase, Class V, type 10D 
                  4.4e−05 
                 25.9 
                 94.9 
                 0.27 
               
               
                 223886_s_at 
                 RNF146 
                 ring finger protein 146 
                  4.7e−05 
                 108.8 
                 295.9 
                 0.37 
               
               
                 230557_at 
                 XRRA1 
                 X-ray radiation resistance associated 1 
                  4.8e−05 
                 33.9 
                 20.2 
                 1.68 
               
               
                 205460_at 
                 NPAS2 
                 neuronal PAS domain protein 2 
                  5.1e−05 
                 31.8 
                 18.6 
                 1.71 
               
               
                 223954_x_at 
                 APBA2BP 
                 amyloid beta (A4) precursor protein- 
                  5.3e−05 
                 126.6 
                 62.8 
                 2.02 
               
               
                   
                   
                 binding, family A, member 2 binding 
               
               
                   
                   
                 protein 
               
               
                 224715_at 
                 WDR34 
                 WD repeat domain 34 
                  5.3e−05 
                 383.8 
                 130.3 
                 2.95 
               
               
                 206875_s_at 
                 SLK 
                 STE20-like kinase (yeast) 
                  5.4e−05 
                 104.1 
                 314.6 
                 0.33 
               
               
                 242935_at 
                 SBF2 
                 SET binding factor 2 
                  5.4e−05 
                 42.5 
                 27.1 
                 1.57 
               
               
                 210588_x_at 
                 HNRPH3 
                 heterogeneous nuclear 
                  5.4e−05 
                 141.1 
                 311.8 
                 0.45 
               
               
                   
                   
                 ribonucleoprotein H3 (2H9) 
               
               
                 201086_x_at 
                 SON 
                 SON DNA binding protein 
                  5.8e−05 
                 318.9 
                 689.4 
                 0.46 
               
               
                 213000_at 
                 MORC3 
                 MORC family CW-type zinc finger 3 
                  5.7e−05 
                 48.6 
                 119.1 
                 0.41 
               
               
                 209285_s_at 
                 C3orf63 
                 chromosome 3 open reading frame 
                  5.9e−05 
                 31.9 
                 87.3 
                 0.37 
               
               
                   
                   
                 63 
               
               
                 213891_s_at 
                   
                 CDNA FLJ37747 fis, clone 
                  5.8e−05 
                 100 
                 435.7 
                 0.23 
               
               
                   
                   
                 BRHIP2022986 
               
               
                 225898_at 
                 WDR54 
                 WD repeat domain 54 
                  5.9e−05 
                 322 
                 131.1 
                 2.46 
               
               
                 212632_at 
                 STX7 
                 Syntaxin 7 
                  6.1e−05 
                 72.6 
                 173.3 
                 0.42 
               
               
                 225050_at 
                 ZNF512 
                 zinc finger protein 512 
                 6.00E−05 
                 48.5 
                 130.1 
                 0.37 
               
               
                 213233_s_at 
                 KLHL9 
                 kelch-like 9 ( Drosophila ) 
                  6.2e−05 
                 135.5 
                 428.4 
                 0.32 
               
               
                 1556316_s_at 
                 LOC284889 
                 hypothetical protein LOC284889 
                  6.4e−05 
                 122.2 
                 34.1 
                 3.58 
               
               
                 211603_s_at 
                 ETV4 
                 ets variant gene 4 (E1A enhancer 
                  6.5e−05 
                 116.2 
                 61 
                 1.90 
               
               
                   
                   
                 binding protein, E1AF) 
               
               
                 213297_at 
                 RMND5B 
                 required for meiotic nuclear division 5 
                  6.6e−05 
                 81.5 
                 49.8 
                 1.64 
               
               
                   
                   
                 homolog B ( S. cerevisiae ) 
               
               
                 218694_at 
                 ARMCX1 
                 armadillo repeat containing, X-linked 1 
                  6.6e−05 
                 35.1 
                 234.3 
                 0.15 
               
               
                 227281_at 
                 SLC29A4 
                 solute carrier family 29 (nucleoside 
                 6.7e−05 
                 83.6 
                 46.3 
                 1.81 
               
               
                   
                   
                 transporters), member 4 
               
               
                 1555788_a_at 
                 TRIB3 
                 tribbles homolog 3 ( Drosophila ) 
                  7.3e−05 
                 49.8 
                 20.3 
                 2.45 
               
               
                 206076_at 
                 LRRC23 
                 leucine rich repeat containing 23 
                  7.4e−05 
                 54.4 
                 28.3 
                 1.92 
               
               
                 209383_at 
                 DDIT3 
                 DNA-damage-inducible transcript 3 
                  7.4e−05 
                 470 
                 182.4 
                 2.58 
               
               
                 225730_s_at 
                 THUMPD3 
                 THUMP domain containing 3 
                  7.5e−05 
                 70 
                 29.7 
                 2.36 
               
               
                 241478_at 
                 MICAL-L2 
                 MICAL-like 2 
                  7.4e−05 
                 102 
                 64.6 
                 1.58 
               
               
                 208676_s_at 
                 PA2G4 
                 proliferation-associated 2G4, 38 kDa 
                  7.5e−05 
                 650.8 
                 267.7 
                 2.43 
               
               
                 241402_at 
                 TSEN54 
                 tRNA splicing endonuclease 54 
                  7.6e−05 
                 72.7 
                 47.1 
                 1.54 
               
               
                   
                   
                 homolog ( S. cerevisiae ) 
               
               
                 208117_s_at 
                 LAS1L 
                 LAS1-like ( S. cerevisiae ) 
                  7.8e−05 
                 312.5 
                 190 
                 1.64 
               
               
                 218061_at 
                 MEA1 
                 male-enhanced antigen 1 
                  7.8e−05 
                 1100.1 
                 583.2 
                 1.89 
               
               
                 218370_s_at 
                 S100PBP 
                 S100P binding protein 
                  7.8e−05 
                 56.7 
                 118.6 
                 0.48 
               
               
                 204413_at 
                 TRAF2 
                 TNF receptor-associated factor 2 
                  7.9e−05 
                 81 
                 51.4 
                 1.58 
               
               
                 228307_at 
                 EMILIN3 
                 elastin microfibril interfacer 3 
                  8.2e−05 
                 58.8 
                 31.2 
                 1.88 
               
               
                 228334_x_at 
                 KIAA1712 
                 KIAA1712 
                  8.1e−05 
                 30.3 
                 92.6 
                 0.33 
               
               
                 208880_s_at 
                 PRPF6 
                 PRP6 pre-mRNA processing factor 6 
                  8.6e−05 
                 429.3 
                 156.1 
                 2.75 
               
               
                   
                   
                 homolog ( S. cerevisiae ) 
               
               
                 212615_at 
                 CHD9 
                 Chromodomain helicase DNA binding 
                  8.5e−05 
                 56.9 
                 185.4 
                 0.31 
               
               
                   
                   
                 protein 9 
               
               
                 201643_x_at 
                 JMJD1B 
                 jumonji domain containing 1B 
                 9.00E−05 
                 160.1 
                 298.1 
                 0.54 
               
               
                 236781_at 
                 ANKS1A 
                 Ankyrin repeat and sterile alpha motif 
                 9.00E−05 
                 35.9 
                 22.4 
                 1.60 
               
               
                   
                   
                 domain containing 1A 
               
               
                 205166_at 
                 CAPN5 
                 calpain 5 
                  9.1e−05 
                 27.1 
                 16.3 
                 1.66 
               
               
                 225838_at 
                 EPC2 
                 enhancer of polycomb homolog 2 
                  9.1e−05 
                 71.1 
                 194.1 
                 0.37 
               
               
                   
                   
                 ( Drosophila ) 
               
               
                 1553778_at 
                 WBSCR27 
                 Williams Beuren syndrome 
                  9.5e−05 
                 67.4 
                 42.3 
                 1.59 
               
               
                   
                   
                 chromosome region 27 
               
               
                 217200_x_at 
                 CYB561 
                 cytochrome b-561 
                  9.6e−05 
                 416.8 
                 191.8 
                 2.17 
               
               
                 206124_s_at 
                 LLGL1 
                 lethal giant larvae homolog 1 
                  9.8e−05 
                 45.1 
                 28.5 
                 1.58 
               
               
                   
                   
                 ( Drosophila ) 
               
               
                 232264_at 
                 EDD1 
                 E3 ubiquitin protein ligase, HECT 
                  9.9e−05 
                 98 
                 31.8 
                 3.08 
               
               
                   
                   
                 domain containing, 1 
               
               
                 241743_at 
                   
                   
                  9.8e−05 
                 39.6 
                 24.2 
                 1.64 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
               
               
             
               
                 TABLE 2 
               
               
                   
               
               
                 Organ 
                   
                   
                   
                   
                   
                   
               
               
                 specific 
                   
                 Gene 
                   
                 Parametric 
                   
                 Gene Ontology Biological 
               
               
                 relapses 
                 Probe set 
                 symbol 
                 Description 
                 p-value 
                 ratio 
                 process and pathway 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                 BONE 
                 221724_s_at 
                 CLEC4A 
                 C-type lectin domain family 4, member A 
                 p &lt; 1e−07 
                 2.45 
                 immune response 
               
               
                   
                 204153_s_at 
                 MFNG 
                 manic fringe homolog ( Drosophila ) 
                 p &lt; 1e−07 
                 2.69 
                 Notch signaling pathway 
               
               
                   
                 208922_s_at 
                 NXF1 
                 nuclear RNA export factor 1 
                 p &lt; 1e−07 
                 1.61 
                 mRNA processing 
               
               
                   
                 227002_at 
                 FAM78A 
                 family with sequence similarity 78, member A 
                 p &lt; 1e−07 
                 2.43 
               
               
                   
                 226245_at 
                 KCTD1 
                 potassium channel tetramerisation domain containing 1 
                 1.00E−07 
                 0.30 
                 potassium ion transport 
               
               
                   
                 227372_s_at 
                 BAIAP2L1 
                 BAI1-associated protein 2-like 1 
                 1.00E−07 
                 0.10 
               
               
                   
                 206060_s_at 
                 PTPN22 
                 protein tyrosine phosphatase, non-receptor type 22 
                 1.00E−07 
                 4.12 
                 signal transduction 
               
               
                   
                   
                   
                 (lymphoid) 
               
               
                   
                 232523_at 
                 MEGF10 
                 MEGF10 protein 
                 1.00E−07 
                 10.77 
               
               
                   
                 222392_x_at 
                 PERP 
                 PERP, TP53 apoptosis effector 
                 1.00E−07 
                 0.09 
                 regulation of apoptosis 
               
               
                   
                 211178_s_at 
                 PSTPIP1 
                 proline-serine-threonine phosphatase interacting protein 1 
                 2.00E−07 
                 3.01 
                 cell adhesion 
               
               
                   
                 204236_at 
                 FLI1 
                 Friend leukemia virus integration 1 
                 2.00E−07 
                 4.80 
                 regulation of transcription 
               
               
                   
                 213290_at 
                 COL6A2 
                 collagen, type VI, alpha 2 
                 2.00E−07 
                 2.63 
                 extracellular matrix 
               
               
                   
                   
                   
                   
                   
                   
                 organization 
               
               
                   
                 203547_at 
                 CD4 
                 CD4 antigen (p55) 
                 2.00E−07 
                 2.62 
                 immune response 
               
               
                   
                 205382_s_at 
                 CFD 
                 complement factor D (adipsin) 
                 2.00E−07 
                 7.37 
                 immune response 
               
               
                   
                 235593_at 
                 ZFHX1B 
                 zinc finger homeobox 1b 
                 2.00E−07 
                 2.92 
                 regulation of transcription 
               
               
                   
                 206120_at 
                 CD33 
                 CD33 antigen (gp67) 
                 3.00E−07 
                 2.33 
                 cell adhesion 
               
               
                   
                 219091_s_at 
                 MMRN2 
                 multimerin 2 
                 4.00E−07 
                 2.96 
               
               
                   
                 214181_x_at 
                 LST1 
                 leukocyte specific transcript 1 
                 4.00E−07 
                 3.87 
                 immune response 
               
               
                   
                 1552667_a_at 
                 SH2D3C 
                 SH2 domain containing 3C 
                 5.00E−07 
                 2.31 
                 intracellular signalling 
               
               
                   
                   
                   
                   
                   
                   
                 cascade 
               
               
                   
                 205326_at 
                 RAMP3 
                 receptor (calcitonin) activity modifying protein 3 
                 5.00E−07 
                 1.95 
                 protein transport 
               
               
                 LUNG 
                 204751_x_at 
                 DSC2 
                 desmocollin 2 
                 p &lt; 
                 8.19 
                 cell adhesion 
               
               
                   
                   
                   
                   
                 0.000001 
               
               
                   
                 223861_at 
                 HORMAD1 
                 HORMA domain containing 1 
                 2.00E−06 
                 21.54 
               
               
                   
                 228171_s_at 
                 PLEKHG4 
                 pleckstrin homology domain containing, family G (with 
                 2.00E−06 
                 2.70 
                 regulation of Rho protein 
               
               
                   
                   
                   
                 RhoGef domain) member 4 
                   
                   
                 signal transduction 
               
               
                   
                 228577_x_at 
                 ODF2L 
                 outer dense fiber of sperm tails 2-like 
                 8.00E−06 
                 2.90 
               
               
                   
                 220941_s_at 
                 C21orf91 
                 chromosome 21 open reading frame 91 
                 1.00E−05 
                 3.60 
               
               
                   
                 227642_at 
                 TFCP2L1 
                 Transcription factor CP2-like 1 
                 1.00E−05 
                 5.50 
                 regulation of transcription 
               
               
                   
                 219867_at 
                 CHODL 
                 chondrolectin 
                 1.40E−05 
                 2.84 
               
               
                   
                 205428_s_at 
                 CALB2 
                 calbindin 2, 29 kDa (calretinin) 
                 1.60E−05 
                 9.20 
                 calcium ion binding 
               
               
                   
                 228956_at 
                 UGT8 
                 UDP glycosyltransferase 8 
                 1.80E−05 
                 15.41 
                 nervous system development 
               
               
                   
                 1554246_at 
                 C1orf210 
                 chromosome 1 open reading frame 210 
                 2.10E−05 
                 2.28 
               
               
                   
                 221705_s_at 
                 SIKE 
                 suppressor of IKK epsilon 
                 2.10E−05 
                 1.85 
               
               
                   
                 211488_s_at 
                 ITGB8 
                 integrin, beta 8 
                 2.60E−05 
                 1.73 
                 cell-matrix adhesion 
               
               
                   
                 213372_at 
                 PAQR3 
                 progestin and adipoQ receptor family member III 
                 2.90E−05 
                 5.64 
               
               
                   
                 208103_s_at 
                 ANP32E 
                 acidic (leucine-rich) nuclear phosphoprotein 32 family, 
                 3.20E−05 
                 5.99 
                 regulation of synaptogenesis 
               
               
                   
                   
                   
                 member E 
               
               
                   
                 60474_at 
                 KIND1 
                 Kindlin 1 
                 3.60E−05 
                 6.87 
                 cell adhesion 
               
               
                   
                 222869_s_at 
                 ELAC1 
                 elaC homolog 1 ( E. coli ) 
                 3.60E−05 
                 1.63 
                 regulation of transcription 
               
               
                   
                 227829_at 
                 GYLTL1B 
                 glycosyltransferase-like 1B 
                 3.90E−05 
                 2.64 
                 synaptic transmission 
               
               
                   
                 226075_at 
                 SPSB1 
                 splA/ryanodine receptor domain and SOCS box 
                 5.60E−05 
                 2.89 
                 intracellular signalling 
               
               
                   
                   
                   
                 containing 1 
                   
                   
                 cascade 
               
               
                   
                 225363_at 
                 PTEN 
                 Phosphatase and tensin homolog (mutated in multiple 
                 6.20E−05 
                 0.41 
                 regulation of cell 
               
               
                   
                   
                   
                 advanced cancers 1) 
                   
                   
                 proliferation/migration 
               
               
                   
                 1553705_a_at 
                 CHRM3 
                 cholinergic receptor, muscarinic 3 
                 7.00E−05 
                 1.84 
                 signal transduction 
               
               
                 LIVER 
                 219682_s_at 
                 TBX3 
                 T-box 3 (ulnar mammary syndrome) 
                 1.00E−07 
                 11.35 
                 regulation of transcription 
               
               
                   
                 221823_at 
                 C5orf30 
                 Chromosome 5 open reading frame 30 
                 1.00E−06 
                 4.59 
               
               
                   
                 221008_s_at 
                 AGXT2L1 
                 alanine-glyoxylate aminotransferase 2-like 1 
                  1.1e−06 
                 3.69 
                 amino acid metabolism 
               
               
                   
                 1557415_s_at 
                 LETM2 
                 Leucine zipper-EF-hand containing transmembrane 
                  1.2e−06 
                 1.87 
               
               
                   
                   
                   
                 protein 2 
               
               
                   
                 228718_at 
                 ZNF44 
                 zinc finger protein 44 (KOX 7) 
                  1.9e−06 
                 2.93 
                 regulation of transcription 
               
               
                   
                 219115_s_at 
                 IL20RA 
                 interleukin 20 receptor, alpha 
                  2.3e−06 
                 3.99 
                 blood coagulation 
               
               
                   
                 226344_at 
                 ZMAT1 
                 zinc finger, matrin type 1 
                  2.6e−06 
                 3.93 
                 nucleotide biosynthesis 
               
               
                   
                 214156_at 
                 MYRIP 
                 myosin VIIA and Rab interacting protein 
                  2.8e−06 
                 3.08 
                 intracellular protein transport 
               
               
                   
                 218173_s_at 
                 WHSC1L1 
                 Wolf-Hirschhorn syndrome candidate 1-like 1 
                  2.9e−06 
                 3.74 
                 regulation of transcription 
               
               
                   
                 225561_at 
                 SELT 
                 selenoprotein T 
                 3.00E−06 
                 4.05 
                 cell redox homeostasis 
               
               
                   
                 209710_at 
                 GATA2 
                 GATA binding protein 2 
                  3.3e−06 
                 4.57 
                 regulation of transcription 
               
               
                   
                 235675_at 
                 DHFRL1 
                 dihydrofolate reductase-like 1 
                 7.00E−06 
                 4.05 
                 nucleotide biosynthesis 
               
               
                   
                 207988_s_at 
                 ARPC2 
                 actin related protein 2/3 complex, subunit 2, 34 kDa 
                 5.00E−06 
                 0.56 
                 cell motility 
               
               
                   
                 217691_x_at 
                 SLC16A3 
                 solute carrier family 16 (monocarboxylic acid transporters), 
                 6.00E−06 
                 0.46 
                 transport 
               
               
                   
                   
                   
                 member 3 
               
               
                   
                 229908_s_at 
                 GNPTG 
                 N-acetylglucosamine-1-phosphate transferase, gamma 
                 7.00E−06 
                 1.83 
                 lysosome 
               
               
                   
                   
                   
                 subunit 
               
               
                   
                 1556308_at 
                 PRRT3 
                 proline-rich transmembrane protein 3 
                 7.00E−06 
                 3.88 
               
               
                   
                 204635_at 
                 RPS6KA5 
                 ribosomal protein S6 kinase, 90 kDa, polypeptide 5 
                 8.00E−06 
                 2.75 
                 regulation of transcription 
               
               
                   
                 227091_at 
                 KIAA1505 
                 KIAA1505 protein 
                 8.00E−06 
                 2.50 
               
               
                   
                 1555982_at 
                 ZFYVE16 
                 Zinc finger, FYVE domain containing 16 
                 9.00E−06 
                 3.97 
                 regulation of endocytosis 
               
               
                   
                 213118_at 
                 KIAA0701 
                 KIAA0701 protein 
                 9.00E−06 
                 2.79 
               
               
                 BRAIN 
                 213483_at 
                 PPWD1 
                 peptidylprolyl isomerase domain and WD repeat 
                 4.00E−07 
                 0.31 
                 protein folding 
               
               
                   
                   
                   
                 containing 1 
               
               
                   
                 210141_s_at 
                 INHA 
                 inhibin, alpha 
                 4.00E−07 
                 1.56 
                 cytokine 
               
               
                   
                 203131_at 
                 PDGFRA 
                 platelet-derived growth factor receptor, alpha polypeptide 
                 5.00E−07 
                 0.06 
                 signal transduction 
               
               
                   
                 226100_at 
                 MLL5 
                 myeloid/lymphoid or mixed-lineage leukemia 5 
                 7.00E−07 
                 0.33 
                 regulation of transcription 
               
               
                   
                 200926_at 
                 RPS23 
                 ribosomal protein S23 
                 1.40E−06 
                 0.58 
                 protein biosynthesis 
               
               
                   
                 224694_at 
                 ANTXR1 
                 anthrax toxin receptor 1 
                 1.50E−06 
                 0.14 
               
               
                   
                 224797_at 
                 ARRDC3 
                 arrestin domain containing 3 
                 1.70E−06 
                 0.17 
               
               
                   
                 207761_s_at 
                 METTL7A 
                 methyltransferase like 7A 
                 3.20E−06 
                 0.15 
               
               
                   
                 235410_at 
                 NPHP3 
                 nephronophthisis 3 (adolescent) 
                 3.70E−06 
                 0.23 
                 kinesin complex 
               
               
                   
                 214154_s_at 
                 PKP2 
                 plakophilin 2 
                 3.90E−06 
                 1.50 
                 cell adhesion 
               
               
                   
                 221780_s_at 
                 DDX27 
                 DEAD (Asp-Glu-Ala-Asp) box polypeptide 27 
                 5.60E−06 
                 2.52 
               
               
                   
                 226839_at 
                 TRA16 
                 TR4 orphan receptor associated protein TRA16 
                 5.90E−06 
                 2.39 
                 signal transduction 
               
               
                   
                 209844_at 
                 HOXB13 
                 homeo box B13 
                 6.40E−06 
                 1.81 
                 regulation of transcription 
               
               
                   
                 220072_at 
                 CSPP1 
                 centrosome and spindle pole associated protein 1 
                 6.50E−06 
                 1.78 
                 microtuble organization 
               
               
                   
                 220965_s_at 
                 RSHL1 
                 radial spokehead-like 1 
                 8.50E−06 
                 1.64 
                 iron homeostasis 
               
               
                   
                 213865_at 
                 DCBLD2 
                 discoidin, CUB and LCCL domain containing 2 
                 9.00E−06 
                 1.90 
                 cell adhesion/wound 
               
               
                   
                   
                   
                   
                   
                   
                 healing 
               
               
                   
                 212106_at 
                 UBXD8 
                 UBX domain containing 8 
                 9.00E−06 
                 2.29 
               
               
                   
                 205224_at 
                 SURF2 
                 surfeit 2 
                 1.00E−05 
                 1.71 
               
               
                   
                 225945_at 
                 ZNF655 
                 zinc finger protein 655 
                 1.00E−05 
                 0.16 
                 regulation of transcription 
               
               
                   
                 206103_at 
                 RAC3 
                 ras-related C3 botulinum toxin substrate 3 
                 1.00E−05 
                 1.89 
                 signal transduction 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
               
               
               
             
               
                 TABLE 3 
               
             
            
               
                   
               
               
                   
                   
                   
                   
                 mean of relative 
                   
                   
                   
               
               
                   
                   
                   
                   
                 esperssion in 
                   
               
               
                 Organ- 
                   
                 Primers (5′-&gt;3′) 
                   
                 other 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 specific 
                 Gene 
                   
                 SEQ ID 
                   
                 SEQ 
                 specific 
                 metastases 
                 p 
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 relapses 
                 symbol 
                 Forward 
                 N o   
                 Reverse 
                 N o   
                 metastases 
                   
                 ratio 
                 value 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 BONE 
                 KCTD1 
                 AAA TAC CCT GAA TCC 
                 1 
                 TGC TGT TTG AGA CTG 
                 2 
                 0.47 
                 0.76 
                 0.62 
                 0.0894 
                   
               
               
                   
                   
                 AGA ATC GGA A 
                   
                 TCCAAA ACA AT 
               
               
                   
               
               
                   
                 BAIAP2L1 
                 AGA CCG CGG CTC CTA 
                 3 
                 AGT CGG GCG GAG TTT 
                 4 
                 0.93 
                 2.08 
                 0.45 
                 0.0250 
               
               
                   
                   
                 ACG AT 
                   
                 CAC AGT 
                   
               
               
                   
               
               
                   
                 PERP 
                 CTG TGG TGG AAA TGC 
                 5 
                 GCT GCT CTA CCC CAC 
                 6 
                 0.34 
                 2.36 
                 0.14 
                 0.0018 
               
               
                   
                   
                 TCC CAA GA 
                   
                 GCG TAC T 
               
               
                   
               
               
                   
                 CFD 
                 ACA GCC AGC CCG ACA 
                 7 
                 TGG CCT TCT CCG ACA 
                 8 
                 2.03 
                 0.22 
                 9.18 
                 0.0012 
               
               
                   
                   
                 CCA T 
                   
                 GCT GTA 
               
               
                   
               
               
                   
                 CD4 
                 GTA CAG CTT CCC AGA 
                 9 
                 CAT TCA GCT TGG ATG 
                 10 
                 7.82 
                 2.09 
                 3.74 
                 0.0022 
               
               
                   
                   
                 AGA AGA GCA TA 
                   
                 GAC CTT TAG T 
               
               
                   
               
               
                   
                 COL6A2 
                 GAA ACA ACA ACT GCC CAG 
                 11 
                 CCG AGG TGT CCA GCA 
                 12 
                 1.35 
                 1.03 
                 1.30 
                 0.0073 
               
               
                   
                   
                 AGA AGA 
                   
                 CGA A 
               
               
                   
               
               
                   
                 FLI1 
                 CCT CAG TTA CCT CAG 
                 13 
                 GGT CGG TGT GGG AGG 
                 14 
                 2.67 
                 0.34 
                 7.81 
                 0.0007 
               
               
                   
                   
                 GGA AAG TTC A 
                   
                 TTG TAT TAT 
               
               
                   
               
               
                   
                 PSTPIP1 
                 CAA GAG TTT GAC CGG 
                 15 
                 CCG CAC TTC CTC GTA 
                 16 
                 5.02 
                 0.84 
                 5.95 
                 0.0018 
               
               
                   
                   
                 CTG ACC AT 
                   
                 GAG CTC AT 
               
               
                   
               
               
                   
                 MEGF10 
                 TGC ACG CGG CAC AGA 
                 17 
                 CCC GCT TTC ATA AAA 
                 18 
                 19.45 
                 0.77 
                 25.26 
                 0.0011 
               
               
                   
                   
                 GTC A TCC AGG ACA 
               
               
                   
               
               
                   
                 PTPN22 
                 ACC ATG GAA AAT TCA 
                 19 
                 GTT TCG CAA AAT TTT 
                 20 
                 10.14 
                 1.72 
                 5.90 
                 0.0012 
               
               
                   
                   
                 ACA TCT TCA A 
                   
                 CAA ACT CTT ACT 
               
               
                   
               
               
                   
                 FAM78A 
                 AGC CAC ATG GAG TTC 
                 21 
                 AGT CGC TGA TGG CTT 
                 22 
                 6.74 
                 1.47 
                 4.59 
                 0.0022 
               
               
                   
                   
                 TAC AAC CAG T 
                   
                 GGA TCT T 
               
               
                   
               
               
                   
                 NXF1 
                 CGA CGT CAA TTC CTT 
                 23 
                 GAA AAA CAC AGC AAT 
                 24 
                 1.53 
                 0.66 
                 2.31 
                 0.0018 
               
               
                   
                   
                 CGT GGT A 
                   
                 GTG CTT GTC T 
               
               
                   
               
               
                   
                 MFNG 
                 CCA GGA CCA GGG AAC 
                 25 
                 CGG AGC AGT TGG TGA 
                 26 
                 1.88 
                 0.62 
                 3.04 
                 0.0056 
               
               
                   
                   
                 AGA CAT T 
                   
                 CCA CA 
               
               
                   
               
               
                   
                 CLEC4A 
                 CAC CAT ACA ATG AAA 
                 27 
                 GGG TGA TTT ACG AAA 
                 28 
                 5.26 
                 0.67 
                 7.91 
                 0.0009 
               
               
                   
                   
                 GTT CCA CAT TCT 
                   
                 ATT TAG CAC AA 
                   
               
               
                   
               
               
                 LUNG 
                 KIND1 
                 AAG GAA CTT GAA CAA 
                 29 
                 GGC ACA ACT TCG CAG 
                 30 
                 4.77 
                 1.08 
                 4.41 
                 0.0404 
               
               
                   
                   
                 GGA GAA CCA CT 
                   
                 CCT CTA 
               
               
                   
               
               
                   
                 ELAC1 
                 AAA GCC AAC TTA AAG CAG 
                 31 
                 AGC CCA GGA AGG CCA 
                 32 
                 0.85 
                 0.67 
                 1.27 
                 0.2220 
               
               
                   
                   
                 GGA GAA T 
                   
                 AAG AA 
               
               
                   
               
               
                   
                 ANP32E 
                 TTT TGA ACT ACT GCA GCA 
                 33 
                 TCA TCT TCA TCG CCA 
                 34 
                 3.84 
                 1.69 
                 2.28 
                 0.0168 
               
               
                   
                   
                 AAT CAC A 
                   
                 TCC TCA T 
               
               
                   
               
               
                   
                 PAQR3 
                 TCG AAG ATG GAT GGC ATT 
                 35 
                 CAA GTA CAC CTG ACG 
                 36 
                 4.01 
                 1.67 
                 2.41 
                 0.1440 
               
               
                   
                   
                 AGA TTA T 
                   
                 CCA GTA GTT AT 
               
               
                   
               
               
                   
                 ITGB8 
                 GAC TGG GCC AAG GTG AAG 
                 37 
                 CCT CTT GAA CAC ACC 
                 38 
                 1.13 
                 0.20 
                 5.67 
                 0.0054 
               
               
                   
                   
                 ACA 
                   
                 ATC CAC ATT 
               
               
                   
               
               
                   
                 C1orf210 
                 GAG GCT GAG ACT CAC 
                 39 
                 CGA AGG CCC AAC AAG 
                 40 
                 1.59 
                 0.99 
                 1.61 
                 0.0797 
               
               
                   
                   
                 TGG TGT CAT 
                   
                 TGT TTT 
               
               
                   
               
               
                   
                 SIKE 
                 CTTGCAACAGGAAAACAG 
                 41 
                 CTG TTT CCG ATA TTT 
                 42 
                 1.22 
                 1.10 
                 1.11 
                 0.7500 
               
               
                   
                   
                 AGAGCTA 
                   
                 GCT CAT GAT AA 
               
               
                   
               
               
                   
                 UGT8 
                 AAA GGC ATG GGG ATA 
                 43 
                 CCC TCT GAC GGT AGC 
                 44 
                 3.40 
                 0.36 
                 9.59 
                 0.0021 
               
               
                   
                   
                 TTG CTA GAA 
                   
                 TGG GAT 
               
               
                   
               
               
                   
                 CALB2 
                 GAA AGG CTC TGG CAT 
                 45 
                 CTG CCA TCT CGA TTT 
                 46 
                 17.30 
                 1.32 
                 13.11 
                 0.1073 
               
               
                   
                   
                 GAT GTC AA 
                   
                 TCC CAT CT 
               
               
                   
               
               
                   
                 CHODL 
                 CTG GAT AGG GCT TTG 
                 47 
                 TTC ATC TGT GTA CCA 
                 48 
                 3.17 
                 0.49 
                 6.51 
                 0.1432 
               
               
                   
                   
                 GAG GAA 
                   
                 GTT TCG GTA CT 
               
               
                   
               
               
                   
                 C21orf91 
                 AAG AAA CAC TCT CCT 
                 49 
                 ATC AGA CTT TGG TAC 
                 50 
                 1.06 
                 0.94 
                 1.12 
                 0.9150 
               
               
                   
                   
                 TCT GCC ACA T 
                   
                 CCC CTC AAT 
               
               
                   
               
               
                   
                 TFCP2L1 
                 CAG TGG CTT CAC CGC 
                 51 
                 TTC AGC AAG TCA GCA 
                 52 
                 2.19 
                 0.29 
                 7.70 
                 0.0005 
               
               
                   
                   
                 AAC A 
                   
                 CCT GAG A 
               
               
                   
               
               
                   
                 ODF2L 
                 CAA ACA AAG GCT TGA 
                 53 
                 GTT TCA GAC AAC TTG 
                 54 
                 1.65 
                 1.42 
                 1.16 
                 1.0000 
               
               
                   
                   
                 CCA TTT TAC A 
                   
                 GCT TCC TGA T 
               
               
                   
               
               
                   
                 HORMAD1 
                 CAA CAT GAA TCT GGG 
                 55 
                 TCC TTT TTG GCA CTG 
                 56 
                 153.90 
                 1.60 
                 96.19 
                 0.0025 
               
               
                   
                   
                 AGA ATA GTC CT 
                   
                 ACT CTT GA 
               
               
                   
               
               
                   
                 PLEKHG4 
                 GGT CTC CGC TGT CCC 
                 57 
                 GAT CTC TGA GTC CTC 
                 58 
                 0.61 
                 0.32 
                 1.91 
                 0.2427 
               
               
                   
                   
                 CTG TA 
                   
                 AGC AGT CAA A 
               
               
                   
               
               
                   
                 DSC2 
                 AAT CAA AGT TTT CAG 
                 59 
                 CGT ACA TGT TCT CCC 
                 60 
                 1.48 
                 0.43 
                 3.41 
                 0.0318 
               
               
                   
                   
                 AAG CCT GGA TA 
                   
                 TCC TTG GT 
               
               
                   
               
               
                 LIVER 
                 GATA2 
                 CAC GAC TAC AGC AGC 
                 61 
                 CAC TCC CGG CCT TCT 
                 62 
                 4.25 
                 2.62 
                 1.62 
                 0.0239 
               
               
                   
                   
                 GGA CTC TT 
                   
                 GAA CA 
               
               
                   
               
               
                   
                 SELT 
                 CTG CTC AAG TTC CAG 
                 63 
                 ATT CTC TCC TTC AAT 
                 64 
                 3.00 
                 2.40 
                 1.25 
                 0.0801 
               
               
                   
                   
                 ATT TGT GTT T 
                   
                 GCG GAT GT 
               
               
                   
               
               
                   
                 WHSC1L1 
                 TAC TAA AAG AGG AAG 
                 65 
                 CCC ACC TTG GAC CAC 
                 66 
                 1.99 
                 0.79 
                 2.52 
                 0.0062 
               
               
                   
                   
                 CCC CAG TTC A 
                   
                 ACA AGA 
               
               
                   
               
               
                   
                 MYRIP 
                 CCA CGA CAA TCC TGC 
                 67 
                 TCC ACT TGC TGC TCA 
                 68 
                 1.21 
                 0.81 
                 1.51 
                 0.1117 
               
               
                   
                   
                 AGA AGA TTA T 
                   
                 CTT TTG CT 
               
               
                   
               
               
                   
                 ZMAT1 
                 GCA AGG AAG TGA ACA 
                 69 
                 AAT CTG CAC ACT CAT 
                 70 
                 1.15 
                 0.99 
                 1.16 
                 0.2267 
               
               
                   
                   
                 TCA AAT TAA AGA A 
                   
                 TTT GGT AAG AGT C 
               
               
                   
               
               
                   
                 IL20RA 
                 ACC TTC CTG TTT CCA 
                 71 
                 GTC ACA CAC TGG GAC 
                 72 
                 0.60 
                 0.33 
                 1.81 
                 0.0563 
               
               
                   
                   
                 TGC AAC AA 
                   
                 CAC GTT CT 
               
               
                   
               
               
                   
                 ZNF44 
                 TCA GGA GAA ATC CAA 
                 73 
                 CAA TAC TAT TTC GAA 
                 74 
                 0.98 
                 0.68 
                 1.45 
                 0.1433 
               
               
                   
                   
                 GGT GTG ATG T 
                   
                 TCT GGC TTA AGG TT 
               
               
                   
               
               
                   
                 LETM2 
                 126 GAC ATT TGG AAC 
                 75 
                 CCC CTT CCT TGG CAA 
                 76 
                 4.69 
                 1.45 
                 3.24 
                 0.0186 
               
               
                   
                 CAA CAA CCT 
                   
                 TTA TTT CAT 
               
               
                   
               
               
                   
                 AGXT2L1 
                 CAG CAA CTC TGC CGG 
                 77 
                 CGT TGG CTT CGG ATC 
                 78 
                 6.57 
                 0.79 
                 8.3 
                 7 0.0091 
               
               
                   
                   
                 AGA AAC T 
                   
                 CTG AAT 
               
               
                   
               
               
                   
                 C5orf30 
                 GAT GCG GAG GAC CGT 
                 79 
                 TCT CTT CAC CTC CTG 
                 80 
                 2.10 
                 1.71 
                 1.23 
                 0.0505 
               
               
                   
                   
                 GTC A 
                   
                 TGC ACT TCT 
               
               
                   
               
               
                   
                 TBX3 
                 CCT CTG ATG AGT CCT 
                 81 
                 CCT CGC TGG GAC ATA 
                 82 
                 2.13 
                 0.68 
                 3.14 
                 0.0075 
               
               
                   
                   
                 CCA GTG AAC A 
                   
                 AAT CTT TGA 
               
               
                   
               
               
                 BRAIN 
                 PPWD1 
                 CTGTGGGTGATGATAAAGCAAT 
                 83 
                 CACTGTCCAGGAAAATAGC 
                 84 
                 0.44 
                 0.92 
                 0.48 
                 0.0260 
               
               
                   
                   
                 GAA 
                   
                 CAAGTT 
               
               
                   
               
               
                   
                 PDGFRA 
                 CAT TTA CAT CTA TGT 
                 85 
                 ATG GCA GAA TCA TCA 
                 86 
                 0.02 
                 0.51 
                 0.05 
                 0.0030 
               
               
                   
                   
                 GCC AGA CCC A 
                   
                 TCC TCC AC 
               
               
                   
               
               
                   
                 MLL5 
                 CGA ATG AAT GTC CAT 
                 87 
                 TCC AGG TGA ACC AGG 
                 88 
                 0.42 
                 0.60 
                 0.71 
                 0.3 700 
               
               
                   
                   
                 CCC CAG ATA 
                   
                 CTT GCT 
               
               
                   
               
               
                   
                 RPS23 
                 GGA ATC GTG CTG GAA 
                 89 
                 CCA TTC TTG ATC AGC 
                 90 
                 0.27 
                 0.54 
                 0.50 
                 0.1600 
               
               
                   
                   
                 AAA GTA GGA GT 
                   
                 TGG ACC CTT A 
               
               
                   
               
               
                   
                 ANTXR1 
                 ATT CCC TGA GCC GCG 
                 91 
                 CAA GGC ATC GAG TTT 
                 92 
                 0.21 
                 0.84 
                 0.24 
                 0.0220 
               
               
                   
                   
                 AAA TCT 
                   
                 TCC CTT GA 
               
               
                   
               
               
                   
                 ARRDC3 
                 TGGGCACGAAAGAGATGATGA 
                 93 
                 GAATGAGGTAGCGAGTGGT 
                 94 
                 0.20 
                 0.49 
                 0.40 
                 0.0120 
               
               
                   
                   
                 TAA 
                   
                 GTCTGT 
               
               
                   
               
               
                   
                 METTL7A 
                 127 GGT GTG CAG AGT 
                 95 
                 ATC CAG GAC TTG TTG 
                 96 
                 0.16 
                 0.65 
                 0.24 
                 0.0240 
               
               
                   
                   
                 GCT GAG A 
                   
                 CCA GAA GTAA T 
               
               
                   
               
               
                   
                 NPHP3 
                 GCA ATG GAG AGA GCA 
                 97 
                 TTC TTT GGT CTC CCT 
                 98 
                 0.29 
                 0.47 
                 0.62 
                 0.3500 
               
               
                   
                   
                 GCA ACA 
                   
                 AAA AAT CTT GA 
               
               
                   
               
               
                   
                 RSHL1 
                 CCA CTT TCA GAA GAT 
                 99 
                 CCA GAG GTT GGA GCG 
                 100 
                 0.37 
                 0.86 
                 0.43 
                 0.6600 
               
               
                   
                   
                 GCA GAA ATC A 
                   
                 CAC A 
               
               
                   
               
               
                   
                 CSPP1 
                 ATG CAG GAA GGT GCC 
                 101 
                 CAC TAG TGT CAT CTC 
                 102 
                 0.94 
                 1.20 
                 0.78 
                 0.6800 
               
               
                   
                   
                 AAA GTT 
                   
                 TGG GCA TTC T 
               
               
                   
               
               
                   
                 HOXB13 
                 GAT GTG TTG CCA GGG 
                 103 
                 GCC CGC TGG AGT CTG 
                 104 
                 34.57 
                 14.75 
                 2.34 
                 0.9400 
               
               
                   
                   
                 AGA ACA GAA 
                   
                 CAA AT 
               
               
                   
               
               
                   
                 TRA16 
                 TGA GTT CAG TGC TGA 
                 105 
                 CTG GGA GGG GCC CTG 
                 106 
                 2.20 
                 1.40 
                 1.57 
                 0.2400 
               
               
                   
                   
                 ATC GCA ACA 
                   
                 GTC T 
               
               
                   
               
               
                   
                 DDX27 
                 CCA GTG AGA GGT CCT 
                 107 
                 AAA GGA AGG GCT AGC 
                 108 
                 3.82 
                 1.87 
                 2.04 
                 0.0450 
               
               
                   
                   
                 GCC AAG A 
                   
                 TCG ATA CTG TT 
               
               
                   
               
               
                   
                 PKP2 
                 CAC CCG AAA GAT GCT 
                 109 
                 AGG GAG AGT TTC TTT 
                 110 
                 0.54 
                 0.38 
                 1.40 
                 0.3000 
               
               
                   
                   
                 GCA TGT T 
                   
                 GGC AAT TTC A 
               
               
                   
               
               
                   
                 INHA 
                 GCC CGA GGA AGA GGA 
                 111 
                 GCC CTC TGG CAG CTG 
                 112 
                 3.06 
                 3.08 
                 0.99 
                 0.3400 
               
               
                   
                   
                 GGA TGT 
                   
                 ACT TGT 
               
               
                   
               
               
                   
                 TBP 
                 TGC ACA GGA GCC AAG 
                 113 
                 CAC ATC ACA GCT CCC 
                 114 
               
               
                   
                   
                 AGT GAA 
                   
                 CAC CA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
             
               
                 TABLE 4 
               
               
                   
               
               
                 Gene symbol 
                 Description 
                 Exemples of Antibodies 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
            
               
                 Bone metastasis associated genes 
               
            
           
           
               
               
               
            
               
                 CLEC4A 
                 C-type lectin domain family 4, member A 
                 Novus biologicals (ab15854); GenWay bitoech (15-288-21195) 
               
               
                 MFNG 
                 manic fringe homolog ( Drosophila ) (secreted Notch ligand) 
                 Abnova (H00004242-M07) 
               
               
                 NXF1 
                 nuclear RNA export factor 1 
                 scbt (sc-17310, sc-32319, sc-25768, sc-28377, sc-17311) 
               
               
                 FAM78A 
                 family with sequence similarity 78, member A 
               
               
                 KCTD1 
                 potassium channel tetramerisation domain containing 1 
               
               
                 BAIAP2L1 
                 BAI1-associated protein 2-like 1 
                 Abnova (H00055971-M01); MBL int. corp (M051-3) 
               
               
                 PTPN22 
                 protein tyrosine phosphatase, non-receptor type 22 (lymphoid) 
                 Abnova (H00026191-M01); R&amp;Dsystems (MAB3428) 
               
               
                 MEGF10 
                 MEGF10 protein 
               
               
                 PERP 
                 TP53 apoptosis effector 
                 Novus biologicals (NB 500-231); Sigma-Aldrich (P5243); 
               
               
                   
                   
                 Research diagnostics (RDI-ALS24284); GenWay bitoech (18- 
               
               
                   
                   
                 661-15116) 
               
               
                 PSTPIP1 
                 proline-serine-threonine phosphatase interacting protein 1 
                 Abnova (H00009051-M01) 
               
            
           
           
               
            
               
                 Osteomimetism associated genes 
               
            
           
           
               
               
               
            
               
                 MMP9 
                 matrix metalloproteinase 9 (gelatinase B, 92 kDa gelatinase, 
                 NeoMarkers (RB-1539) 
               
               
                   
                 92 kDa type IV collagenase) 
               
               
                 IBSP 
                 integrin-binding sialoprotein (bone sialoprotein, bone 
                 Usbiological (S1013-34B) 
               
               
                   
                 sialoprotein II) 
               
               
                 OMD 
                 osteomodulin 
                 Abnova (H00004958-A01) 
               
               
                 COMP 
                 cartilage oligomeric matrix protein 
                 AbCam (ab11056) 
               
               
                 MEPE 
                 matrix, extracellular phosphoglycoprotein with ASARM motif 
                 R&amp;Dsystems (AF3140) 
               
               
                   
                 (bone) 
               
            
           
           
               
            
               
                 Lung metastasis associated genes (highest ranking genes) 
               
            
           
           
               
               
               
            
               
                 DSC2 
                 desmocollin 2 
                 scbt (sc-34308, sc-34311, sc-34312); Progen Biotechnik (GP542, 
               
               
                   
                   
                 610120); Research diagnostics (RDI-PRO610120, RDI- 
               
               
                   
                   
                 PROGP542); UsBiological (D3221-50) 
               
               
                 HORMAD1 
                 HORMA domain containing 1 
                 Abnova (H00084072-M01) 
               
            
           
           
               
               
            
               
                 PLEKHG4 
                 pleckstrin homology domain containing, family G (with RhoGef domain) member 4 
               
            
           
           
               
               
               
            
               
                 ODF2L 
                 outer dense fiber of sperm tails 2-like 
                   
               
               
                 C21orf91 
                 chromosome 21 open reading frame 91 
               
               
                 TFCP2L1 
                 Transcription factor CP2-like 1 
                 Abcam (ab3962), Novus biological (NB 600-22), Eurogentec 
               
               
                   
                   
                 (24220), Imgenex (IMG-4094) 
               
               
                 CHODL 
                 chondrolectin 
                 R&amp;Dsystems (AF2576); Abnova (H00140578-A01) 
               
               
                 CALB2 
                 calbindin 2, 29 kDa (calretinin) 
                 Chemicon (AB5054); Usbiological (C1036-01M) 
               
            
           
           
               
               
            
               
                 UGT8 
                 UDP glycosyltransferase 8 (UDP-galactose ceramide galactosyltransferase) 
               
            
           
           
               
               
               
            
               
                 C1orf210 
                 chromosome 1 open reading frame 210 
                   
               
               
                 SIKE 
                 suppressor of IKK epsilon 
               
               
                 ITGB8 
                 integrin, beta 8 
                 Abnova (H00003696-M01, H00003696-A01); GenWay biotech 
               
               
                   
                   
                 (15-288-21362); sctb (sc-10817, sc-25714, sc-6638) 
               
               
                 PAQR3 
                 progestin and adipoQ receptor family member III 
               
               
                 ANP32E 
                 acidic (leucine-rich) nuclear phosphoprotein 32 family, member 
                 GenWay biotech (A21207), UsBiological (L1238) 
               
               
                   
                 E 
               
               
                 KIND1 
                 kindlin 
                 Abcam (ab24152); sctb (sc-30854) 
               
               
                 ELAC1 
                 elaC homolog 1 ( E. coli ) 
                 Abnova (H00055520-A01) 
               
               
                 GYLTL1B 
                 glycosyltransferase-like 1B 
               
            
           
           
               
            
               
                 Liver metastasis associated genes 
               
            
           
           
               
               
               
            
               
                 TBX3 
                 T-box 3 (ulnar mammary syndrome) 
                 Abnova (H00006926-A01) 
               
               
                 C5orf30 
                 hypothetical gene supported by AF038182; BC009203 
               
            
           
           
               
               
            
               
                 AGXT2L1 
                 alanine-glyoxylate aminotransferase 2-like 1///alanine-glyoxylate aminotransferase 2-like 1 
               
            
           
           
               
               
               
            
               
                 LETM2 
                 Leucine zipper-EF-hand containing transmembrane protein 2 
                   
               
               
                 ZNF44 
                 zing finger protein 44 
               
               
                 IL20RA 
                 interleukin 20 receptor, alpha 
                 LifeSpan biosciences (LS-C722) 
               
               
                 ZMAT1 
                 Zinc finger, matrin type 1 
               
               
                 MYRIP 
                 myosin VIIA and Rab interacting protein 
                 Novus Biologicals (NB 100-1278); Everest biotech Ltd (EB06023) 
               
               
                 WHSC1L1 
                 Wolf-Hirschhorn syndrome candidate 1-like 1 
                 Abcam (ab4514); BioCat (AP1904a-AB) 
               
               
                 SELT 
                 selenoprotein T 
               
               
                 GATA2 
                 GATA binding protein 2 
                 Abnova (H00002624-M01); R&amp;Dsystems (AF2046) 
               
               
                 DHFRL1 
                 dihydrofolate reductase-like 1 
               
               
                 ARPC2 
                 actin related protein 2/3 complex, subunit 2, 34 kDa 
               
            
           
           
               
               
            
               
                 SLC16A3 
                 solute carrier family 16 (monocarboxylic acid transporters), member 3 
               
            
           
           
               
               
               
            
               
                 GNPTG 
                   
                   
               
               
                 PRRT3 
               
               
                 RPS6KA5 
                 ribosomal protein S6 kinase, 90 kDa, polypeptide 5 
                 Santa cruz (sc-2591, sc-9392, sc-25417); R&amp;Dsystems (AF2518) 
               
            
           
           
               
            
               
                 Brain metastasis associated genes 
               
            
           
           
               
               
            
               
                 PPWD1 
                 peptidylprolyl isomerase domain and WD repeat containing 1 
               
            
           
           
               
               
               
            
               
                 INHA 
                 Inhibin, alpha 
                 AbCam (Ab10599) 
               
               
                 PDGFRA 
                 platelet-derived growth factor receptor, alpha polypeptide 
                 Abnova (H00005156-M01) 
               
               
                 MLL5 
                 myeloid/lymphoid or mixed-lineage leukemia 5 (trithorax 
                 Abgent (AP6186a); Orbigen (PAB-10849) 
               
               
                   
                 homolog,  Drosophila ) 
               
               
                 RPS23 
                 ribosomal protein S23 
                 Abnova (H00006228-A01) 
               
               
                 ANTXR1 
                 Anthrax toxin receptor 1 
                 AbCam (Ab21270) 
               
               
                 ARRDC3 
                 arrestin domain containing 3 
               
               
                 METTL7A 
                 methyltransferase like 7A 
               
               
                 NPHP3 
                 nephronophthisis 3 (adolescent) 
               
               
                 PKP2 
                 plakophilin 2 
                 Novus biologicals (ab19469) 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 5 
               
             
            
               
                   
               
               
                 Lung metastasis associated genes obtained from a class comparison of lung (n = 5) and non-lung metastases of breast cancer (n = 18) 
               
            
           
           
               
               
               
               
               
               
            
               
                   
                 Gene 
                   
                   
                   
                 Parametric 
               
               
                 Probe Set 
                 Symbol 
                 Gene Title 
                 Function/biological process 
                 Fold change 
                 p-value 
               
               
                   
               
            
           
           
               
               
               
               
               
               
            
               
                 204751_x_at 
                 DSC2* 
                 desmocollin 2 
                 Cell adhesion 
                 8.2 
                 p &lt; 0.000001 
               
               
                 223861_at 
                 HORMAD1* 
                 HORMA domain containing 1 
                   
                 21.5 
                 2.00E−06 
               
               
                 228171_s_at 
                 PLEKHG4* 
                 pleckstrin homology domain containing, 
                 Rho protein signal transduction 
                 2.7 
                 2.00E−06 
               
               
                   
                   
                 family G, member 4 
               
               
                 228577_x_at 
                 ODF2L* 
                 outer dense fiber of sperm tails 2-like 
                   
                 2.9 
                 8.00E−06 
               
               
                 220941_s_at 
                 C21orf91* 
                 chromosome 21 open reading frame 91 
                   
                 3.6 
                 1.00E−05 
               
               
                 227642_at 
                 TFCP2L1* 
                 Transcription factor CP2-like 1 
                 Regulation of transcription 
                 5.5 
                 1.00E−05 
               
               
                 219867_at 
                 CHODL* 
                 chondrolectin 
                 Hyaluronic acid binding 
                 2.8 
                 1.40E−05 
               
               
                 205428_s_at 
                 CALB2* 
                 calbindin 2, 29 kDa (calretinin) 
                 Calcium ion binding 
                 9.2 
                 1.60E−05 
               
               
                 228956_at 
                 UGT8* 
                 UDP glycosyltransferase 8 
                 Glycosphingolipid biosynthetic process 
                 15.4 
                 1.80E−05 
               
               
                 1554246_at 
                 C1orf210* 
                 chromosome 1 open reading frame 210 
                   
                 2.3 
                 2.10E−05 
               
               
                 221705_s_at 
                 SIKE* 
                 suppressor of IKK epsilon 
                   
                 1.9 
                 2.10E−05 
               
               
                 211488_s_at 
                 ITGB8* 
                 integrin, beta 8 
                 Cell adhesion/Signal transduction 
                 1.7 
                 2.60E−05 
               
               
                 213372_at 
                 PAQR3* 
                 progestin and adipoQ receptor family 
                 Receptor activity 
                 5.6 
                 2.90E−05 
               
               
                   
                   
                 member III 
               
               
                 208103_s_at 
                 ANP32E* 
                 acidic (leucine-rich) nuclear phosphoprotein 
                 Phosphatase inhibitor activity 
                 6.0 
                 3.20E−05 
               
               
                   
                   
                 32 family, member E 
               
               
                 60474_at 
                 FERMT1* 
                 Fermitin family homolog 1 ( drosophila ) 
                 Cell adhesion 
                 6.9 
                 3.60E−05 
               
               
                 222869_s_at 
                 ELAC1* 
                 elaC homolog 1 ( E. coli ) 
                 tRNA processing 
                 1.6 
                 3.60E−05 
               
               
                 227829_at 
                 GYLTL1B 
                 glycosyltransferase-like 1B 
                 Glycosphingolipid biosynthetic process 
                 2.6 
                 3.90E−05 
               
               
                 226075_at 
                 SPSB1 
                 splA/ryanodine receptor domain and SOCS 
                 Intracellular signalling cascade 
                 2.9 
                 5.60E−05 
               
               
                   
                   
                 box containing 1 
               
               
                 1553705_a_at 
                 CHRM3 
                 cholinergic receptor, muscarinic 3 
                 G-protein coupled signal transduction 
                 2.0 
                 6.10E−05 
               
               
                 225363_at 
                 PTEN 
                 Phosphatase and tensin homolog (mutated 
                 Phosphatidylinositol signalling 
                 0.4 
                 6.20E−05 
               
               
                   
                   
                 in multiple advanced cancers 1) 
               
               
                 203256_at 
                 CDH3 
                 cadherin 3, type 1, P-cadherin (placental) 
                 Cell adhesion 
                 6.1 
                 9.50E−05 
               
               
                   
               
               
                 *Genes tested by qRT-PCR. Colored lines correspond to genes that were validated (Mann-Whitney U test) 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 6 
               
             
            
               
                   
               
               
                 Association between clinical and pathological characteristics and the 
               
               
                 6-gene classifier among 72 lymph node-negative patients treated at CRH 
               
            
           
           
               
               
               
            
               
                   
                 6-gene classification 
                   
               
            
           
           
               
               
               
               
               
            
               
                   
                 All patients 
                 High Risk group 
                 Low Risk group 
                   
               
               
                 Characteristics 
                 (n = 72) 
                 (n = 18) 
                 (n = 54) 
                 P value* 
               
               
                   
               
            
           
           
               
               
               
               
               
               
            
               
                 Metastases within 10 years 
                   
                   
                   
                   
                 0.79 
               
               
                 yes 
                 38 (53%) 
                 10 
                 (56%) 
                 28 (52%) 
               
               
                 no 
                 34 (47%) 
                 8 
                 (44%) 
                 26 (48%) 
               
               
                 Lung metastases within 10 years 
                   
                   
                   
                   
                 0.04 
               
               
                 yes 
                 11 (15%) 
                 6 
                 (33%) 
                 5 (9%) 
               
               
                 no 
                 61 (85%) 
                 12 
                 (67%) 
                 49 (91%) 
               
               
                 Menopausal status 
                   
                   
                   
                   
                 0.58 
               
               
                 Pre 
                 18 (31%) 
                 6 
                 (40%) 
                 12 (28%) 
               
               
                 Post 
                 40 (69%) 
                 9 
                 (60%) 
                 31 (72%) 
               
               
                 Macroscopic tumor size 
                   
                   
                   
                   
                 0.59 
               
               
                 ≦20 mm 
                 23 (33%) 
                 5 
                 (28%) 
                 18 (35%) 
               
               
                 &gt;20 mm 
                 47 (67%) 
                 13 
                 (72%) 
                 34 (65%) 
               
               
                 SBR histological grade 
                   
                   
                   
                   
                 0.01 
               
               
                 I 
                  7 (11%) 
                 0 
                 (0%) 
                  7 (15%) 
               
               
                 II 
                 37 (60%) 
                 7 
                 (44%) 
                 30 (65%) 
               
               
                 III 
                 18 (29%) 
                 9 
                 (56%) 
                  9 (20%) 
               
               
                 Estrogen receptor status 
                   
                   
                   
                   
                 &lt;0.001 
               
               
                 Positive 
                 44 (61%) 
                 3 
                 (17%) 
                 41 (76%) 
               
               
                 Negative 
                 28 (39%) 
                 15 
                 (83%) 
                 13 (24%) 
               
               
                 Progesterone receptor 
                   
                   
                   
                   
                 0.004 
               
               
                 Positive 
                 37 (51%) 
                 4 
                 (22%) 
                 33 (61%) 
               
               
                 Negative 
                 35 (49%) 
                 14 
                 (78%) 
                 21 (39%) 
               
               
                   
               
               
                 *Chi 2  test 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 7 
               
             
            
               
                   
               
               
                 Multivariate analysis for lung metastasis 
               
               
                 in 721 breast cancer patients 
               
            
           
           
               
               
               
               
            
               
                 Variable 
                 Hazard Ratio 
                 95% C.I 
                 P value 
               
               
                   
               
               
                 6-gene signature (pos. vs. neg.) 
                 2.12 
                  1.2-3.76 
                 0.01 
               
               
                 ER negative (yes vs. no) 
                 1.83 
                 1.03-3.26 
                 0.04 
               
               
                 Lymph node positive (yes vs. no) 
                 0.92 
                 0.52-1.62 
                 0.77 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 8 
               
             
            
               
                   
               
               
                 Highest ranking genes obtained from a class comparison of bone and nonbone metastases of breast cancer (n = 23) 
               
            
           
           
               
               
               
               
               
               
            
               
                 Probe Set 
                 Gene 
                 Gene Title 
                 Function/biological process 
                 Fold change 
                 p value 
               
               
                   
               
            
           
           
               
               
               
               
               
               
            
               
                 204679_at 
                 KCNK1 
                 potassium channel, subfamily K, 
                 potassium ion transport 
                 0.06 
                 p &lt; 1e−07 
               
               
                   
                   
                 member 1 
               
               
                 221724_s_at 
                 CLEC4A 
                 C-type lectin domain family 4, member A 
                 immune response/cell adhesion/signal transduction 
                 2.45 
                 p &lt; 1e−07 
               
               
                 204153_s_at 
                 MFNG 
                 manic fringe homolog ( Drosophila ) 
                 Notch signaling pathway 
                 2.69 
                 p &lt; 1e−07 
               
               
                 208922_s_at 
                 NXF1 
                 nuclear RNA export factor 1 
                 mRNA transport 
                 1.61 
                 p &lt; 1e−07 
               
               
                 206060_s_at 
                 PTPN22 
                 protein tyrosine phosphatase, non-receptor 
                 tyrosine phosphatase activity/signal transduction 
                 4.12 
                 1.00E−07 
               
               
                   
                   
                 type 22 
               
               
                 222392_x_at 
                 PERP 
                 PERP, TP53 apoptosis effector 
                 cell adhesion/apoptosis 
                 0.09 
                 1.00E−07 
               
               
                 211178_s_at 
                 PSTPIP1 
                 proline-serine-threonine phosphatase 
                 cell adhesion/signal transduction 
                 3.01 
                 2.00E−07 
               
               
                   
                   
                 interacting protein 1 
               
               
                 204236_at 
                 FLI1 
                 Friend leukemia virus integration 1 
                 regulation of transcription 
                 4.80 
                 2.00E−07 
               
               
                 213290_at 
                 COL6A2 
                 collagen, type VI, alpha 2 
                 cell adhesion/extracellular matrix organization 
                 2.63 
                 2.00E−07 
               
               
                 203547_at 
                 CD4 
                 CD4 antigen (p55) 
                 immune response/cell adhesion/signaling pathway 
                 2.62 
                 2.00E−07 
               
               
                 205382_s_at 
                 CFD 
                 D component of complement (adipsin) 
                 immune response 
                 7.37 
                 2.00E−07 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 9 
               
             
            
               
                   
               
               
                 Predictive analysis of the lung metastasis-specific 
               
               
                 markers on the patients cohort named EMC-344 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                 Parametric 
                   
                 Hazard 
                 Cox regression 
                 SD of log 
                   
                 Gene 
               
               
                   
                 p-value 
                 FDR 
                 Ratio 
                 coefficient 
                 intensities 
                 Probe set 
                 symbol 
               
               
                   
                   
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                 1 
                 0.0011233 
                 0.0258359 
                 1.429 
                 0.357 
                 1.36 
                 208103_s_at 
                 ANP32E 
               
               
                 2 
                 0.0033469 
                 0.0384893 
                 1.705 
                 0.534 
                 0.894 
                 221505_at 
                 ANP32E 
               
               
                 3 
                 0.0160063 
                 0.122715 
                 1.347 
                 0.298 
                 1.172 
                 204751_x_at 
                 DSC2 
               
               
                 4 
                 0.0435256 
                 0.2502722 
                 1.669 
                 0.512 
                 0.639 
                 213372_at 
                 PAQR3 
               
               
                 5 
                 0.0635786 
                 0.2512905 
                 1.241 
                 0.216 
                 1.347 
                 219867_at 
                 CHODL 
               
               
                 6 
                 0.0791345 
                 0.2512905 
                 1.361 
                 0.308 
                 0.855 
                 219735_s_at 
                 TFCP2L1 
               
               
                 7 
                 0.0862416 
                 0.2512905 
                 0.693 
                 −0.367 
                 0.695 
                 221705_s_at 
                 SIKE 
               
               
                 8 
                 0.0874054 
                 0.2512905 
                 1.588 
                 0.462 
                 0.59 
                 219677_at 
                 SPSB1 
               
               
                 9 
                 0.1819305 
                 0.4021895 
                 1.153 
                 0.142 
                 1.308 
                 205428_s_at 
                 CALB2 
               
               
                 10 
                 0.182647 
                 0.4021895 
                 0.818 
                 −0.201 
                 1.154 
                 222176_at 
                 PTEN 
               
               
                 11 
                 0.2246446 
                 0.4021895 
                 0.834 
                 −0.182 
                 0.865 
                 204054_at 
                 PTEN 
               
               
                 12 
                 0.2258217 
                 0.4021895 
                 0.853 
                 −0.159 
                 1.081 
                 204666_s_at 
                 SIKE 
               
               
                 13 
                 0.2273245 
                 0.4021895 
                 0.761 
                 −0.273 
                 0.628 
                 211711_s_at 
                 PTEN 
               
               
                 14 
                 0.3015296 
                 0.4953701 
                 1.125 
                 0.118 
                 1.355 
                 60474_at 
                 C20orf42 
               
               
                 15 
                 0.337911 
                 0.5128545 
                 1.213 
                 0.193 
                 0.804 
                 220941_s_at 
                 C21orf91 
               
               
                 16 
                 0.3616357 
                 0.5128545 
                 1.086 
                 0.083 
                 1.621 
                 218796_at 
                 C20orf42 
               
               
                 17 
                 0.3790664 
                 0.5128545 
                 1.059 
                 0.057 
                 2.435 
                 203256_at 
                 CDH3 
               
               
                 18 
                 0.4986762 
                 0.6371974 
                 1.069 
                 0.067 
                 1.488 
                 208358_s_at 
                 UGT8 
               
               
                 19 
                 0.57957 
                 0.7011632 
                 0.855 
                 −0.157 
                 0.538 
                 204053_x_at 
                 PTEN 
               
               
                 20 
                 0.6097071 
                 0.7011632 
                 1.046 
                 0.045 
                 1.737 
                 204750_s_at 
                 DSC2 
               
               
                 21 
                 0.7965431 
                 0.8593998 
                 0.926 
                 −0.077 
                 0.511 
                 204665_at 
                 SIKE 
               
               
                 22 
                 0.830164 
                 0.8593998 
                 1.037 
                 0.036 
                 0.918 
                 211488_s_at 
                 ITGB8 
               
               
                 23 
                 0.8593998 
                 0.8593998 
                 1.023 
                 0.023 
                 1.224 
                 205816_at 
                 ITGB8 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 9 
               
             
            
               
                   
               
               
                 Description of the markers of Table 9 
               
            
           
           
               
               
               
               
            
               
                   
                   
                 Gene 
                   
               
               
                   
                 Probe set 
                 symbol 
                 Description 
               
               
                   
                   
               
            
           
           
               
               
               
               
            
               
                 1 
                 208103_s_at 
                 ANP32E 
                 acidic (leucine-rich) nuclear phosphoprotein 32 family, member E 
               
               
                 2 
                 221505_at 
                 ANP32E 
                 acidic (leucine-rich) nuclear phosphoprotein 32 family, member E 
               
               
                 3 
                 204751_x_at 
                 DSC2 
                 desmocollin 2 
               
               
                 4 
                 213372_at 
                 PAQR3 
                 progestin and adipoQ receptor family member III 
               
               
                 5 
                 219867_at 
                 CHODL 
                 chondrolectin 
               
               
                 6 
                 219735_s_at 
                 TFCP2L1 
                 transcription factor CP2-like 1 
               
               
                 7 
                 221705_s_at 
                 SIKE 
                 suppressor of IKK epsilon 
               
               
                 8 
                 219677_at 
                 SPSB1 
                 splA/ryanodine receptor domain and SOCS box containing 1 
               
               
                 9 
                 205428_s_at 
                 CALB2 
                 calbindin 2, 29 kDa (calretinin) 
               
               
                 10 
                 222176_at 
                 PTEN 
                 phosphatase and tensin homolog (mutated in multiple advanced 
               
               
                   
                   
                   
                 cancers 1) 
               
               
                 11 
                 204054_at 
                 PTEN 
                 phosphatase and tensin homolog (mutated in multiple advanced 
               
               
                   
                   
                   
                 cancers 1) 
               
               
                 12 
                 204666_s_at 
                 SIKE 
                 suppressor of IKK epsilon 
               
               
                 13 
                 211711_s_at 
                 PTEN 
                 phosphatase and tensin homolog (mutated in multiple advanced 
               
               
                   
                   
                   
                 cancers 1) 
               
               
                 14 
                 60474_at 
                 C20orf42 
                 chromosome 20 open reading frame 42 
               
               
                 15 
                 220941_s_at 
                 C21orf91 
                 chromosome 21 open reading frame 91 
               
               
                 16 
                 218796_at 
                 C20orf42 
                 chromosome 20 open reading frame 42 
               
               
                 17 
                 203256_at 
                 CDH3 
                 cadherin 3, type 1, P-cadherin (placental) 
               
               
                 18 
                 208358_s_at 
                 UGT8 
                 UDP glycosyltransferase 8 (UDP-galactose ceramide 
               
               
                   
                   
                   
                 galactosyltransferase) 
               
               
                 19 
                 204053_x_at 
                 PTEN 
                 phosphatase and tensin homolog (mutated in multiple advanced 
               
               
                   
                   
                   
                 cancers 1) 
               
               
                 20 
                 204750_s_at 
                 DSC2 
                 desmocollin 2 
               
               
                 21 
                 204665_at 
                 SIKE 
                 suppressor of IKK epsilon 
               
               
                 22 
                 211488_s_at 
                 ITGB8 
                 integrin, beta 8 
               
               
                 23 
                 205816_at 
                 ITGB8 
                 integrin, beta 8 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 10 
               
               
                   
               
             
            
               
                 Predictive analysis of the lung metastasis-specific markers on the patients cohort named MSK-82 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                 Parametric 
                   
                   
                 Cox regression 
                 SD of log 
                   
                   
               
               
                   
                 p-value 
                 FDR 
                 Hazard Ratio 
                 coefficient 
                 intensities 
                 Probe set 
                 Gene symbol 
               
               
                   
               
               
                 1 
                 0.0003892 
                 0.0089516 
                 2.08 
                 0.732 
                 0.87 
                 205428_s_at 
                 CALB2 
               
               
                 2 
                 0.0014922 
                 0.0171603 
                 5.219 
                 1.652 
                 0.332 
                 60474_at 
                 C20orf42 
               
               
                 3 
                 0.0024355 
                 0.0186722 
                 2.107 
                 0.745 
                 0.877 
                 204751_x_at 
                 DSC2 
               
               
                 4 
                 0.0050329 
                 0.0289392 
                 4.095 
                 1.410 
                 0.426 
                 219677_at 
                 SPSB1 
               
               
                 5 
                 0.0099859 
                 0.0459351 
                 1.838 
                 0.609 
                 0.945 
                 208103_s_at 
                 ANP32E 
               
               
                 6 
                 0.0121753 
                 0.046672 
                 3.967 
                 1.378 
                 0.548 
                 204053_x_at 
                 PTEN 
               
               
                 7 
                 0.0180818 
                 0.0594116 
                 2.72 
                 1.001 
                 0.483 
                 218796_at 
                 C20orf42 
               
               
                 8 
                 0.0492486 
                 0.1415897 
                 1.513 
                 0.414 
                 1.255 
                 203256_at 
                 CDH3 
               
               
                 9 
                 0.0588468 
                 0.1475319 
                 1.957 
                 0.671 
                 0.587 
                 219735_s_at 
                 TFCP2L1 
               
               
                 10 
                 0.0641443 
                 0.1475319 
                 3.023 
                 1.106 
                 0.358 
                 204750_s_at 
                 DSC2 
               
               
                 11 
                 0.0775927 
                 0.1622393 
                 2.493 
                 0.913 
                 0.422 
                 219867_at 
                 CHODL 
               
               
                 12 
                 0.1165306 
                 0.2233503 
                 2.037 
                 0.711 
                 0.561 
                 211711_s_at 
                 PTEN 
               
               
                 13 
                 0.1297388 
                 0.2295379 
                 1.524 
                 0.421 
                 1.021 
                 221505_at 
                 ANP32E 
               
               
                 14 
                 0.1614638 
                 0.265262 
                 2.049 
                 0.717 
                 0.373 
                 213372_at 
                 PAQR3 
               
               
                 15 
                 0.1929821 
                 0.2959059 
                 5.224 
                 1.653 
                 0.193 
                 204665_at 
                 SIKE 
               
               
                 16 
                 0.2148451 
                 0.3088398 
                 2.501 
                 0.917 
                 0.324 
                 220941_s_at 
                 C21orf91 
               
               
                 17 
                 0.4649749 
                 0.6290837 
                 1.541 
                 0.432 
                 0.385 
                 208358_s_at 
                 UGT8 
               
               
                 18 
                 0.5784291 
                 0.7391039 
                 2.4 
                 0.875 
                 0.163 
                 205816_at 
                 ITGB8 
               
               
                 19 
                 0.6368802 
                 0.7709602 
                 1.543 
                 0.434 
                 0.24 
                 204666_s_at 
                 SIKE 
               
               
                 20 
                 0.6705386 
                 0.7711194 
                 1.302 
                 0.264 
                 0.417 
                 204054_at 
                 PTEN 
               
               
                 21 
                 0.7563827 
                 0.8013443 
                 1.474 
                 0.388 
                 0.218 
                 211488_s_at 
                 ITGB8 
               
               
                 22 
                 0.7683003 
                 0.8013443 
                 1.4 
                 0.336 
                 0.224 
                 221705_s_at 
                 SIKE 
               
               
                 23 
                 0.8013443 
                 0.8013443 
                 0.547 
                 −0.603 
                 0.118 
                 222176_at 
                 PTEN 
               
               
                   
               
            
           
           
               
            
               
                 Description of the markers of Table 10 
               
            
           
           
               
               
               
               
            
               
                   
                 Probe set 
                 Gene symbol 
                 Description 
               
               
                   
               
               
                 1 
                 205428_s_at 
                 CALB2 
                 calbindin 2, 29 kDa (calretinin) 
               
               
                 2 
                 60474_at 
                 C20orf42 
                 chromosome 20 open reading frame 42 
               
               
                 3 
                 204751_x_at 
                 DSC2 
                 desmocollin 2 
               
               
                 4 
                 219677_at 
                 SPSB1 
                 sp1A/ryanodine receptor domain and SOCS box containing 1 
               
               
                 5 
                 208103_s_at 
                 ANP32E 
                 acidic (leucine-rich) nuclear phosphoprotein 32 family, member E 
               
               
                 6 
                 204053_x_at 
                 PTEN 
                 phosphatase and tensin homolog (mutated in multiple advanced cancers 
               
               
                   
                   
                   
                 1) 
               
               
                 7 
                 218796_at 
                 C20orf42 
                 chromosome 20 open reading frame 42 
               
               
                 8 
                 203256_at 
                 CDH3 
                 cadherin 3, type 1, P-cadherin (placental) 
               
               
                 9 
                 219735_s_at 
                 TFCP2L1 
                 transcription factor CP2-like 1 
               
               
                 10 
                 204750_s_at 
                 DSC2 
                 desmocollin 2 
               
               
                 11 
                 219867_at 
                 CHODL 
                 chondrolectin 
               
               
                 12 
                 211711_s_at 
                 PTEN 
                 phosphatase and tensin homolog (mutated in multiple advanced cancers 
               
               
                   
                   
                   
                 1) 
               
               
                 13 
                 221505_at 
                 ANP32E 
                 acidic (leucine-rich) nuclear phosphoprotein 32 family, member E 
               
               
                 14 
                 213372_at 
                 PAQR3 
                 progestin and adipoQ receptor family member III 
               
               
                 15 
                 204665_at 
                 SIKE 
                 suppressor of IKK epsilon 
               
               
                 16 
                 220941_s_at 
                 C21orf91 
                 chromosome 21 open reading frame 91 
               
               
                 17 
                 208358_s_at 
                 UGT8 
                 UDP glycosyltransferase 8 (UDP-galactose ceramide 
               
               
                   
                   
                   
                 galactosyltransferase) 
               
               
                 18 
                 205816_at 
                 ITGB8 
                 integrin, beta 8 
               
               
                 19 
                 204666_s_at 
                 SIKE 
                 suppressor of IKK epsilon 
               
               
                 20 
                 204054_at 
                 PTEN 
                 phosphatase and tensin homolog (mutated in multiple advanced cancers 
               
               
                   
                   
                   
                 1) 
               
               
                 21 
                 211488_s_at 
                 ITGB8 
                 integrin, beta 8 
               
               
                 22 
                 221705_s_at 
                 SIKE 
                 suppressor of IKK epsilon 
               
               
                 23 
                 222176_at 
                 PTEN 
                 phosphatase and tensin homolog (mutated in multiple advanced cancers 
               
               
                   
                   
                   
                 1) 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 11 
               
             
            
               
                   
               
               
                 Predictive analysis of the lung metastasis-specific markers on the patients cohort named NKI-295 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                   
                 Parametric 
                   
                   
                 Cox regression 
                 SD of log 
                   
                   
                   
                   
               
               
                   
                 p-value 
                 FDR 
                 Hazard Ratio 
                 coefficient 
                 intensities 
                 Unique id 
                 GB acc 
                 UG cluster 
                 Gene symbol 
               
               
                   
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 1 
                 0.0108108 
                 0.1949653 
                 3.108 
                 1.134 
                 0.403 
                 12233 
                 NM_014553 
                 Hs.119903 
                 TFCP2L1 
               
               
                 2 
                 0.0419568 
                 0.1949653 
                 3.946 
                 1.373 
                 0.262 
                 5151 
                 X56807 
                 Hs.95612 
                 DSC2 
               
               
                 3 
                 0.0432328 
                 0.1949653 
                 0.115 
                 −2.163 
                 0.21 
                 13428 
                 Contig39922_RC 
                 Hs.86543 
                 GYLTL1B 
               
               
                 4 
                 0.0450324 
                 0.01949653 
                 3.656 
                 1.296 
                 0.275 
                 15800 
                 Contig46362_RC 
                 Hs.119903 
                 TFCP2L1 
               
               
                 5 
                 0.0528812 
                 0.1949653 
                 3.024 
                 1.107 
                 0.327 
                 17349 
                 Contig49790_RC 
                 Hs.95612 
                 DSC2 
               
               
                 6 
                 0.0584896 
                 0.1949653 
                 2.259 
                 0.815 
                 0.372 
                 10488 
                 NM_007088 
                 Hs.106857 
                 CALB2 
               
               
                 7 
                 0.0686958 
                 0.1962737 
                 9.446 
                 2.246 
                 0.141 
                 23624 
                 NM_000740 
                 Hs.7138 
                 CHRM3 
               
               
                 8 
                 0.0907955 
                 0.2269888 
                 2.069 
                 0.727 
                 0.381 
                 1386 
                 NM_001740 
                 Hs.106857 
                 CALB2 
               
               
                 9 
                 0.1562884 
                 0.3473076 
                 3.029 
                 1.108 
                 0.248 
                 4995 
                 AL117435 
                 Hs.188781 
                 PLEKHG4 
               
               
                 10 
                 0.2539722 
                 0.4661338 
                 2.258 
                 0.814 
                 0.23 
                 2764 
                 NM_003360 
                 Hs.274293 
                 UGT8 
               
               
                 11 
                 0.2841824 
                 0.4661338 
                 0.259 
                 −1.351 
                 0.151 
                 20423 
                 NM_000314 
                 Hs.253309 
                 PTEN 
               
               
                 12 
                 0.3003186 
                 0.4661338 
                 2.578 
                 0.947 
                 0.185 
                 19915 
                 NM_017671 
                 Hs.180479 
                 C20orf42 
               
               
                 13 
                 0.302987 
                 0.4661338 
                 3.476 
                 1.246 
                 0.13 
                 20151 
                 Contig39667_RC 
                 Hs.293811 
                 C21orf91 
               
               
                 14 
                 0.3494798 
                 0.4943692 
                 2.038 
                 0.712 
                 0.264 
                 14424 
                 AL137342 
                 Hs.274293 
                 UGT8 
               
               
                 15 
                 0.3707769 
                 0.4943692 
                 3.365 
                 1.213 
                 0.151 
                 7655 
                 AF131840 
                 Hs.458389 
                 SPSB1 
               
               
                 16 
                 0.4670792 
                 0.583849 
                 1.397 
                 0.334 
                 0.421 
                 1529 
                 NM_001793 
                 Hs.191842 
                 CDH3 
               
               
                 17 
                 0.6470609 
                 0.7612481 
                 2.004 
                 0.695 
                 0.116 
                 18301 
                 NM_017447 
                 Hs.293811 
                 C21orf91 
               
               
                 18 
                 0.7465434 
                 0.8294927 
                 0.655 
                 −0.423 
                 0.157 
                 12394 
                 Contig33904_RC 
                 Hs.283725 
                 CHODL 
               
               
                 19 
                 0.8698028 
                 0.8848604 
                 0.765 
                 −0.268 
                 0.114 
                 22398 
                 NM_018696 
                 Hs.47572 
                 ELAC1 
               
               
                 20 
                 0.8848604 
                 0.8848604 
                 0.876 
                 −0.132 
                 0.197 
                 24006 
                 NM_002214 
                 Hs.355722 
                 ITGB8 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 12 
               
               
                   
               
             
            
               
                 Predictive analysis of the bone metastasis-specific markers on the patients cohort named NKI-295 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                 Parametric p- 
                   
                   
                 Cox regression 
                 SD of log 
                   
                   
               
               
                   
                 value 
                 FDR 
                 Hazard Ratio 
                 coefficient 
                 intensities 
                 Probe set 
                 Gene symbol 
               
               
                   
               
               
                 1 
                 0.0014664 
                 0.0762528 
                 4.082 
                 1.407 
                 0.443 
                 210629_x_at 
                 LST1 
               
               
                 2 
                 0.0070981 
                 0.1002536 
                 5.055 
                 1.620 
                 0.32 
                 204236_at 
                 FLI1 
               
               
                 3 
                 0.0095354 
                 0.1002536 
                 2.566 
                 0.942 
                 0.565 
                 214181_x_at 
                 LST1 
               
               
                 4 
                 0.0104244 
                 0.1002536 
                 3.094 
                 1.129 
                 0.398 
                 203603_s_at 
                 ZEB2 
               
               
                 5 
                 0.0115734 
                 0.1002536 
                 3.664 
                 1.299 
                 0.432 
                 214574_x_at 
                 LST1 
               
               
                 6 
                 0.0135848 
                 0.1002536 
                 3.417 
                 1.229 
                 0.435 
                 211582_x_at 
                 LST1 
               
               
                 7 
                 0.0159031 
                 0.1002536 
                 3.717 
                 1.313 
                 0.399 
                 215633_x_at 
                 LST1 
               
               
                 8 
                 0.0165012 
                 0.1002536 
                 2.377 
                 0.866 
                 0.576 
                 219892_at 
                 TM6SF1 
               
               
                 9 
                 0.0179101 
                 0.1002536 
                 1.911 
                 0.648 
                 0.653 
                 219947_at 
                 CLEC4A 
               
               
                 10 
                 0.0197086 
                 0.1002536 
                 4.627 
                 1.532 
                 0.342 
                 211581_x_at 
                 LST1 
               
               
                 11 
                 0.0212075 
                 0.1002536 
                 2.838 
                 1.043 
                 0.435 
                 221724_s_at 
                 CLEC4A 
               
               
                 12 
                 0.0286492 
                 0.1241465 
                 7.748 
                 2.047 
                 0.324 
                 201234_at 
                 ILK 
               
               
                 13 
                 0.0328336 
                 0.1313344 
                 8.671 
                 2.160 
                 0.25 
                 210786_s_at 
                 FLI1 
               
               
                 14 
                 0.0391372 
                 0.133966 
                 1.46 
                 0.378 
                 1.247 
                 205382_s_at 
                 CFD 
               
               
                 15 
                 0.0402882 
                 0.133966 
                 0.483 
                 −0.728 
                 0.94 
                 204678_s_at 
                 KCNK1 
               
               
                 16 
                 0.0412203 
                 0.133966 
                 1.725 
                 0.545 
                 0.829 
                 213125_at 
                 OLFML2B 
               
               
                 17 
                 0.0479453 
                 0.1466562 
                 1.777 
                 0.575 
                 0.583 
                 205326_at 
                 RAMP3 
               
               
                 18 
                 0.0628825 
                 0.1816606 
                 0.311 
                 −1.168 
                 0.68 
                 211056_s_at 
                 SRD5A1 
               
               
                 19 
                 0.0718102 
                 0.1965332 
                 2.457 
                 0.899 
                 0.485 
                 213290_at 
                 COL6A2 
               
               
                 20 
                 0.0794813 
                 0.2066514 
                 0.598 
                 −0.514 
                 1.02 
                 204679_at 
                 KCNK1 
               
               
                 21 
                 0.1353711 
                 0.3352046 
                 2.9 
                 1.065 
                 0.322 
                 211178_s_at 
                 PSTPIP1 
               
               
                 22 
                 0.1495017 
                 0.3390126 
                 3.198 
                 1.163 
                 0.299 
                 206120_at 
                 CD33 
               
               
                 23 
                 0.1499479 
                 0.3390126 
                 2.876 
                 1.056 
                 0.329 
                 204153_s_at 
                 MFNG 
               
               
                 24 
                 0.1698972 
                 0.3681106 
                 1.426 
                 0.355 
                 0.863 
                 202803_s_at 
                 ITGB2 
               
               
                 25 
                 0.1801727 
                 0.3738658 
                 2.869 
                 1.054 
                 0.28 
                 204152_s_at 
                 MFNG 
               
               
                 26 
                 0.1869329 
                 0.3738658 
                 0.599 
                 −0.512 
                 0.985 
                 204675_at 
                 SRD5A1 
               
               
                 27 
                 0.2215229 
                 0.3957445 
                 0.029 
                 −3.540 
                 0.11 
                 216424_at 
                 CD4 
               
               
                 28 
                 0.2236087 
                 0.3957445 
                 0.442 
                 −0.816 
                 0.681 
                 203426_s_at 
                 IGFBP5 
               
               
                 29 
                 0.2247289 
                 0.3957445 
                 0.702 
                 −0.354 
                 1.162 
                 211958_at 
                 IGFBP5 
               
               
                 30 
                 0.2287178 
                 0.3957445 
                 0.465 
                 −0.766 
                 0.638 
                 203424_s_at 
                 IGFBP5 
               
               
                 31 
                 0.2359246 
                 0.3957445 
                 2.613 
                 0.960 
                 0.334 
                 208922_s_at 
                 NXF1 
               
               
                 32 
                 0.2553002 
                 0.4137783 
                 0.457 
                 −0.783 
                 0.715 
                 210959_s_at 
                 SRD5A1 
               
               
                 33 
                 0.2625901 
                 0.4137783 
                 0.405 
                 −0.904 
                 0.723 
                 207370_at 
                 IBSP 
               
               
                 34 
                 0.2831181 
                 0.4330042 
                 0.508 
                 −0.677 
                 0.461 
                 220966_x_at 
                 ARPC5L 
               
               
                 35 
                 0.2917092 
                 0.4333965 
                 0.696 
                 −0.362 
                 1.082 
                 203425_s_at 
                 IGFBP5 
               
               
                 36 
                 0.3194611 
                 0.4610668 
                 0.28 
                 −1.273 
                 0.773 
                 204712_at 
                 WIF1 
               
               
                 37 
                 0.3316346 
                 0.4610668 
                 1.386 
                 0.326 
                 0.806 
                 209156_s_at 
                 COL6A2 
               
               
                 38 
                 0.3369334 
                 0.4610668 
                 1.925 
                 0.655 
                 0.368 
                 219091_s_at 
                 MMRN2 
               
               
                 39 
                 0.3501288 
                 0.4668384 
                 0.826 
                 −0.191 
                 1.406 
                 217744_s_at 
                 PERP 
               
               
                 40 
                 0.3756809 
                 0.4883852 
                 0.848 
                 −0.165 
                 1.532 
                 203936_s_at 
                 MMP9 
               
               
                 41 
                 0.4433208 
                 0.5622605 
                 1.464 
                 0.381 
                 0.51 
                 203547_at 
                 CD4 
               
               
                 42 
                 0.5021384 
                 0.6216952 
                 2.053 
                 0.719 
                 0.194 
                 208010_s_at 
                 PTPN22 
               
               
                 43 
                 0.5822182 
                 0.7021499 
                 1.511 
                 0.413 
                 0.371 
                 221565_s_at 
                 FAM26B 
               
               
                 44 
                 0.5941268 
                 0.7021499 
                 0.89 
                 −0.117 
                 1.233 
                 211959_at 
                 IGFBP5 
               
               
                 45 
                 0.633394 
                 0.731922 
                 1.382 
                 0.324 
                 0.353 
                 206060_s_at 
                 PTPN22 
               
               
                 46 
                 0.662699 
                 0.749138 
                 1.246 
                 0.220 
                 0.491 
                 205908_s_at 
                 OMD 
               
               
                 47 
                 0.7906842 
                 0.8747995 
                 0.752 
                 −0.285 
                 0.252 
                 215104_at 
                 NRIP2 
               
               
                 48 
                 0.9126254 
                 0.9839027 
                 1.084 
                 0.081 
                 0.381 
                 57715_at 
                 FAM26B 
               
               
                 49 
                 0.9310478 
                 0.9839027 
                 0.869 
                 −0.140 
                 0.171 
                 215639_at 
                 SH2D3C 
               
               
                 50 
                 0.9460603 
                 0.9839027 
                 1.074 
                 0.071 
                 0.269 
                 213783_at 
                 MFNG 
               
               
                 51 
                 0.976646 
                 0.9957959 
                 0.985 
                 −0.015 
                 0.558 
                 205907_s_at 
                 OMD 
               
               
                   
               
            
           
           
               
            
               
                 Description of the markers of Table 12 
               
            
           
           
               
               
               
               
            
               
                   
                 Probe set 
                 Gene symbol 
                 Description 
               
               
                   
               
               
                 1 
                 210629_x_at 
                 LST1 
                 leukocyte specific transcript 1 
               
               
                 2 
                 204236_at 
                 FLI1 
                 Friend leukemia virus integration 1 
               
               
                 3 
                 214181_x_at 
                 LST1 
                 leukocyte specific transcript 1 
               
               
                 4 
                 203603_s_at 
                 ZEB2 
                 zinc finger E-box binding homeobox 2 
               
               
                 5 
                 214574_x_at 
                 LST1 
                 leukocyte specific transcript 1 
               
               
                 6 
                 211582_x_at 
                 LST1 
                 leukocyte specific transcript 1 
               
               
                 7 
                 215633_x_at 
                 LST1 
                 leukocyte specific transcript 1 
               
               
                 8 
                 219892_at 
                 TM6SF1 
                 transmembrane 6 superfamily member 1 
               
               
                 9 
                 219947_at 
                 CLEC4A 
                 C-type lectin domain family 4, member A 
               
               
                 10 
                 211581_x_at 
                 LST1 
                 leukocyte specific transcript 1 
               
               
                 11 
                 221724_s_at 
                 CLEC4A 
                 C-type lectin domain family 4, member A 
               
               
                 12 
                 201234_at 
                 ILK 
                 integrin-linked kinase 
               
               
                 13 
                 210786_s_at 
                 FLI1 
                 Friend leukemia virus integration 1 
               
               
                 14 
                 205382_s_at 
                 CFD 
                 complement factor D (adipsin) 
               
               
                 15 
                 204678_s_at 
                 KCNK1 
                 potassium channel, subfamily K, member 1 
               
               
                 16 
                 213125_at 
                 OLFML2B 
                 olfactomedin-like 2B 
               
               
                 17 
                 205326_at 
                 RAMP3 
                 receptor (G protein-coupled) activity modifying protein 3 
               
               
                 18 
                 211056_s_at 
                 SRD5A1 
                 steroid-5-alpha-reductase, alpha polypeptide 1 (3-oxo-5 alpha-steroid delta 4-dehydrogenase 
               
               
                   
                   
                   
                 alpha 1) 
               
               
                 19 
                 213290_at 
                 COL6A2 
                 collagen, type VI, alpha 2 
               
               
                 20 
                 204679_at 
                 KCNK1 
                 potassium channel, subfamily K, member 1 
               
               
                 21 
                 211178_s_at 
                 PSTPIP1 
                 proline-serine-threonine phosphatase interacting protein 1 
               
               
                 22 
                 206120_at 
                 CD33 
                 CD33 molecule 
               
               
                 23 
                 204153_s_at 
                 MFNG 
                 MFNG O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase 
               
               
                 24 
                 202803_s_at 
                 ITGB2 
                 integrin, beta 2 (complement component 3 receptor 3 and 4 subunit) 
               
               
                 25 
                 204152_s_at 
                 MFNG 
                 MFNG O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase 
               
               
                 26 
                 204675_at 
                 SRD5A1 
                 steroid-5-alpha-reductase, alpha polypeptide 1 (3-oxo-5 alpha-steroid delta 4-dehydrogenase 
               
               
                   
                   
                   
                 alpha 1) 
               
               
                 27 
                 216424_at 
                 CD4 
                 CD4 molecule 
               
               
                 28 
                 203426_s_at 
                 IGFBP5 
                 insulin-like growth factor binding protein 5 
               
               
                 29 
                 211958_at 
                 IGFBP5 
                 insulin-like growth factor binding protein 5 
               
               
                 30 
                 203424_s_at 
                 IGFBP5 
                 insulin-like growth factor binding protein 5 
               
               
                 31 
                 208922_s_at 
                 NXF1 
                 nuclear RNA export factor 1 
               
               
                 32 
                 210959_s_at 
                 SRD5A1 
                 steroid-5-alpha-reductase, alpha polypeptide 1 (3-oxo-5 alpha-steroid delta 4-dehydrogenase 
               
               
                   
                   
                   
                 alpha 1) 
               
               
                 33 
                 207370_at 
                 IBSP 
                 integrin-binding sialoprotein (bone sialoprotein, bone sialoprotein II) 
               
               
                 34 
                 220966_x_at 
                 ARPC5L 
                 actin related protein 2/3 complex, subunit 5-like 
               
               
                 35 
                 203425_s_at 
                 IGFBP5 
                 insulin-like growth factor binding protein 5 
               
               
                 36 
                 204712_at 
                 WIF1 
                 WNT inhibitory factor 1 
               
               
                 37 
                 209156_s_at 
                 COL6A2 
                 collagen, type VI, alpha 2 
               
               
                 38 
                 219091_s_at 
                 MMRN2 
                 multimerin 2 
               
               
                 39 
                 217744_s_at 
                 PERP 
                 PERP, TP53 apoptosis effector 
               
               
                 40 
                 203936_s_at 
                 MMP9 
                 matrix metallopeptidase 9 (gelatinase B, 92 kDa gelatinase, 92 kDa type IV collagenase) 
               
               
                 41 
                 203547_at 
                 CD4 
                 CD4 molecule 
               
               
                 42 
                 208010_s_at 
                 PTPN22 
                 protein tyrosine phosphatase, non-receptor type 22 (lymphoid) 
               
               
                 43 
                 221565_s_at 
                 FAM26B 
                 family with sequence similarity 26, member B 
               
               
                 44 
                 211959_at 
                 IGFBP5 
                 insulin-like growth factor binding protein 5 
               
               
                 45 
                 206060_s_at 
                 PTPN22 
                 protein tyrosine phosphatase, non-receptor type 22 (lymphoid) 
               
               
                 46 
                 205908_s_at 
                 OMD 
                 osteomodulin 
               
               
                 47 
                 215104_at 
                 NRIP2 
                 nuclear receptor interacting protein 2 
               
               
                 48 
                 57715_at 
                 FAM26B 
                 family with sequence similarity 26, member B 
               
               
                 49 
                 215639_at 
                 SH2D3C 
                 SH2 domain containing 3C 
               
               
                 50 
                 213783_at 
                 MFNG 
                 MFNG O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase 
               
               
                 51 
                 205907_s_at 
                 OMD 
                 osteomodulin 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 13 
               
             
            
               
                   
               
               
                 Highest ranking genes obtained from a class comparison of 
               
               
                 bone and non-bone metastases of breast cancer (n = 23) 
               
            
           
           
               
               
               
               
               
            
               
                 Probe Set 
                 Gene 
                 Gene Title 
                 Fold 
                 p value 
               
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 203936_s_at 
                 MMP9 
                 matrix metallopeptidase 9 
                 36.73 
                 p &lt; 1e−07 
               
               
                 204679_at 
                 KCNK1 
                 potassium channel, subfamily K, member 1 
                 0.06 
                 p &lt; 1e−07 
               
               
                 236028_at 
                 IBSP 
                 Integrin-binding sialoprotein (bone sialoprotein) 
                 123.76 
                 p &lt; 1e−07 
               
               
                 205907_s_at 
                 OMD 
                 osteomodulin 
                 41.31 
                 p &lt; 1e−07 
               
               
                 221724_s_at 
                 CLEC4A 
                 C-type lectin domain family 4, member A 
                 2.45 
                 p &lt; 1e−07 
               
               
                 204153_s_at 
                 MFNG 
                 manic fringe homolog ( Drosophila ) 
                 2.69 
                 p &lt; 1e−07 
               
               
                 57715_at 
                 FAM26B 
                 family with sequence similarity 26, member B 
                 2.29 
                 p &lt; 1e−07 
               
               
                 226914_at 
                 ARPC5L 
                 actin related protein 2/3 complex, subunit 5-like 
                 0.35 
                 p &lt; 1e−07 
               
               
                 208922_s_at 
                 NXF1 
                 nuclear RNA export factor 1 
                 1.61 
                 p &lt; 1e−07 
               
               
                 227002_at 
                 FAM78A 
                 family with sequence similarity 78, member A 
                 2.43 
                 p &lt; 1e−07 
               
               
                 226245_at 
                 KCTD1 
                 potassium channel tetramerisation domain containing 1 
                 0.31 
                 1.00E−07 
               
               
                 227372_s_at 
                 BAIAP2L1 
                 BAI1-associated protein 2-like 1 
                 0.10 
                 1.00E−07 
               
               
                 206060_s_at 
                 PTPN22 
                 protein tyrosine phosphatase, non-receptor type 22 
                 4.12 
                 1.00E−07 
               
               
                 232523_at 
                 MEGF10 
                 MEGF10 protein 
                 10.78 
                 1.00E−07 
               
               
                 222392_x_at 
                 PERP 
                 PERP, TP53 apoptosis effector 
                 0.09 
                 1.00E−07 
               
               
                 231879_at 
                 COL12A1 
                 collagen, type XII, alpha 1 
                 8.35 
                 1.00E−07 
               
               
                 211178_s_at 
                 PSTPIP1 
                 proline-serine-threonine phosphatase interacting protein 1 
                 3.01 
                 2.00E−07 
               
               
                 204236_at 
                 FLI1 
                 Friend leukemia virus integration 1 
                 4.80 
                 2.00E−07 
               
               
                 213290_at 
                 COL6A2 
                 collagen, type VI, alpha 2 
                 2.63 
                 2.00E−07 
               
               
                 203547_at 
                 CD4 
                 CD4 antigen (p55) 
                 2.62 
                 2.00E−07 
               
               
                 205382_s_at 
                 CFD 
                 D component of complement (adipsin) 
                 7.37 
                 2.00E−07 
               
               
                 204712_at 
                 WIF1 
                 WNT inhibitory factor 1 
                 25.94 
                 2.00E−07 
               
               
                 235593_at 
                 ZEB2 
                 zinc finger homeobox 1b 
                 2.92 
                 2.00E−07 
               
               
                 206120_at 
                 CD33 
                 CD33 antigen (gp67) 
                 2.33 
                 3.00E−07 
               
               
                 232204_at 
                 EBF 
                 early B-cell factor 
                 5.00 
                 4.00E−07 
               
               
                 219091_s_at 
                 MMRN2 
                 multimerin 2 
                 2.96 
                 4.00E−07 
               
               
                 214181_x_at 
                 LST1 
                 leukocyte specific transcript 1 
                 3.87 
                 4.00E−07 
               
               
                 211958_at 
                 IGFBP5 
                 insulin-like growth factor binding protein 5 
                 4.04 
                 4.00E−07 
               
               
                 1552667_a_at 
                 SH2D3C 
                 SH2 domain containing 3C 
                 2.31 
                 5.00E−07 
               
               
                 205326_at 
                 RAMP3 
                 receptor (calcitonin) activity modifying protein 3 
                 1.95 
                 5.00E−07 
               
               
                 202803_s_at 
                 ITGB2 
                 integrin, beta 2 (antigen CD18 (p95) 
                 8.33 
                 5.00E−07 
               
               
                 201234_at 
                 ILK 
                 integrin-linked kinase 
                 2.22 
                 5.00E−07 
               
               
                 227243_s_at 
                 EBF3 
                 early B-cell factor 3 
                 3.70 
                 6.00E−07 
               
               
                 219892_at 
                 TM6SF1 
                 transmembrane 6 superfamily member 1 
                 5.42 
                 6.00E−07 
               
               
                 215104_at 
                 NRIP2 
                 nuclear receptor interacting protein 2 
                 1.34 
                 7.00E−07 
               
               
                 223245_at 
                 STRBP 
                 spermatid perinuclear RNA binding protein 
                 0.29 
                 8.00E−07 
               
               
                 226345_at 
                 ARL8 
                 ADP-ribosylation factor-like 8 
                 0.31 
                 9.00E−07 
               
               
                 204675_at 
                 SRD5A1 
                 steroid-5-alpha-reductase, alpha polypeptide 1 
                 0.15 
                 9.00E−07 
               
               
                 225373_at 
                 C10orf54 
                 chromosome 10 open reading frame 54 
                 3.10 
                 9.00E−07 
               
               
                 213125_at 
                 OLFML2B 
                 olfactomedin-like 2B 
                 8.01 
                 9.00E−07