Patent Abstract:
The present invention provides a method for assessing the prognosis of Ewing&#39;s Sarcoma patients comprising determining the expression pattern of a defined set of genes in tumor material obtained from said patients, and assigning said expression pattern to either a good prognosis or poor prognosis group.

Full Description:
FIELD OF THE INVENTION 
       [0001]    The present invention relates to a method for assessing prognosis in cancer patients. More specifically, the invention disclosed hereinbelow provides a genetic analysis technique that may be used to assess the prognosis of patients with Ewing Sarcoma. 
       BACKGROUND OF THE INVENTION 
       [0002]    Ewing&#39;s Sarcoma (ES) is the second most common primary malignant bone tumor in children and adolescents and it belongs to a group of neuroectodermal tumors known as Ewing&#39;s Sarcoma Family of Tumors (EFT). This is an aggressive tumor with a high propensity for recurrence and distant metastases [Ginsberg, J. P. et al. “Ewing sarcoma family of tumors: Ewing&#39;s sarcoma of bone and soft tissue and the peripheral primitive neuroectodermal tumors.” In: Principles and Practice of Pediatric Oncology, (eds.: Pizzo, P. A. &amp; Poplack) 4th edition, 973-1016, Philadelphia, Pa., 2002]. 
         [0003]    All EFT share specific translocations resulting in the fusion of the EWS gene on chromosome 22q12 with different ETS oncogenes on different chromosomes; the most frequent (˜95%) is FLI1 on chromosome 11. These translocations are considered distinct diagnostic features of ES tumors [Delattre, O. et al.,  New Eng. J. Med.  331, 294-299 (1994)]. 
         [0004]    Both the primary site of the tumor, and the initial response to therapy (assessed histologically as the degree of tumor necrosis following surgery), have become accepted valid prognostic factors in localized tumors. In spite of advances in multimodal therapy, including combination of aggressive chemotherapy, radiotherapy and surgery, about 50% of patients eventually relapse, even after 5 years [Terrier, P. et al.,  Semin. Diagn. Pathol.  13, 250-257 
         [0005]    Current clinical and biological characteristics fail to accurately classify ES patients according to their clinical behavior, and it is therefore essential to search for novel reliable prognostic parameters, already at diagnosis. 
         [0006]    It is therefore a purpose of the present invention to provide a genetic profiling method for prognosis assessment of patients presenting with ES. 
         [0007]    It is another purpose of the invention to provide materials and kits for performing the aforementioned method. 
         [0008]    Further objects and advantages of the present invention will become apparent as the description proceeds. 
       SUMMARY OF THE INVENTION 
       [0009]    It has now been found that it is possible to distinguish between ES patients having a good prognosis and those having a poor prognosis by means of comparing gene expression patterns in nucleic acid material isolated from the tumors of said patients. Furthermore, it has been found that this prognosis determination may be performed very early on, during initial diagnosis. 
         [0010]    The present invention is primarily directed to a method for assessing the prognosis of ES patients comprising determining the expression pattern of a defined set of genes in tumor material obtained from said patients, and assigning said expression pattern to either a good prognosis or poor prognosis group. 
         [0011]    The term “good prognosis” is used herein to indicate that the patients are not expected to show ES-related signs, symptoms or evidence for a period of time compatible with the usual clinical meaning of the term. In many cases, this may be taken to mean that the patient is expected to be free from ES-related symptoms for at least five years from assessment. The term “poor prognosis” is similarly used to indicate that the patients are expected to relapse during treatment or within the first few years following treatment. 
         [0012]    The term “expression pattern” is used herein to refer to the overall profile of results obtained when the expression of a defined set of genes is determined. Such a pattern is advantageous since it facilitates the use of both quantitative, statistical analytical techniques as well as permitting rapid visual inspection and comparison of results. Preferably (but not exclusively) such a pattern is obtained by the use of a matrix method, such as a high density microarray method. 
         [0013]    Although any suitable technique may be used to determine the expression of the aforementioned defined set of genes, in one preferred embodiment of the method, this technique is a nucleic acid hybridization technique. 
         [0014]    In a particularly preferred embodiment, the nucleic acid hybridization technique comprises the steps of extracting total RNA from the ES-patient tumor material, generating double-stranded cDNA from said total RNA, performing in vitro transcription of said cDNA, labeling the RNA transcript obtained thereby, preparing a hybridization mix comprising said labeled RNA transcript together with irrelevant and control nucleic acid sequences, hybridization of said hybridization mix to a solid-state human genome microarray and generating and amplifying a hybridization signal. This hybridization signal provides a visual expression pattern which may then be assigned to one of the good or poor prognosis groups. 
         [0015]    In another preferred embodiment, the hybridization technique used is selected from the group consisting of northern blotting and western blotting. 
         [0016]    In other preferred embodiments of the invention, gene expression may be determined by the use of a technique other than a hybridization technique. In a particularly preferred embodiment, the technique is selected from the group consisting of RT-PCR, semi-quantitative RT-PCR, quantitative real time RT-PCR, immunohistochemistry and ELISA. 
         [0017]    In one particularly preferred embodiment of the method of the invention, the assignment of the gene expression pattern to one of the good or poor prognosis groups is performed by means of a hierarchical clustering technique. 
         [0018]    In one preferred embodiment of the method of the invention, the aforementioned defined set of genes comprises genes selected from the group of 818 genes listed in table 1, hereinbelow. 
         [0019]    In another preferred embodiment, the defined set of genes consists of between 1 and 100 genes selected from the aforementioned group of 818 genes. 
         [0020]    In another preferred embodiment, the defined set of genes consists of between 101 and 200 genes selected from the aforementioned group of 818 genes. 
         [0021]    In another preferred embodiment, the defined set of genes consists of between 201 and 300 genes selected from the aforementioned group of 818 genes. 
         [0022]    In another preferred embodiment, the defined set of genes consists of between 301 and 400 genes selected from the aforementioned group of 818 genes. 
         [0023]    In another preferred embodiment, the defined set of genes consists of between 401 and 500 genes selected from the aforementioned group of 818 genes. 
         [0024]    In another preferred embodiment, the defined set of genes consists of between 501 and 600 genes selected from the aforementioned group of 818 genes. 
         [0025]    In another preferred embodiment, the defined set of genes consists of between 601 and 700 genes selected from the aforementioned group of 818 genes. 
         [0026]    In another preferred embodiment, the defined set of genes consists of between 701 and 818 genes selected from the aforementioned group of 818 genes. 
         [0027]    In another aspect, the present invention is also directed to a solid-state nucleic acid microarray comprising at least two nucleic acids affixed to a substrate, wherein each of said at least two nucleic acids consists of a partial sequence of one of the genes present in the aforementioned group of 818 genes. 
         [0028]    In one preferred embodiment, the microarray of the present invention comprises between 2 and 100 nucleic acid sequences, wherein each of said sequences consists of a partial sequence of one of the genes present in the aforementioned group of 818 genes. 
         [0029]    In another preferred embodiment, the microarray of the present invention comprises between 101 and 200 nucleic acid sequences, wherein each of said sequences consists of a partial sequence of one of the genes present in the aforementioned group of 818 genes. 
         [0030]    In another preferred embodiment, the microarray of the present invention comprises between 201 and 300 nucleic acid sequences, wherein each of said sequences consists of a partial sequence of one of the genes present in the aforementioned group of 818 genes. 
         [0031]    In another preferred embodiment, the microarray of the present invention comprises between 301 and 400 nucleic acid sequences, wherein each of said sequences consists of a partial sequence of one of the genes present in the aforementioned group of 818 genes. 
         [0032]    In another preferred embodiment, the microarray of the present invention comprises between 401 and 500 nucleic acid sequences, wherein each of said sequences consists of a partial sequence of one of the genes present in the aforementioned group of 818 genes. 
         [0033]    In another preferred embodiment, the microarray of the present invention comprises between 501 and 600 nucleic acid sequences, wherein each of said sequences consists of a partial sequence of one of the genes present in the aforementioned group of 818 genes. 
         [0034]    In another preferred embodiment, the microarray of the present invention comprises between 601 and 700 nucleic acid sequences, wherein each of said sequences consists of a partial sequence of one of the genes present in the aforementioned group of 818 genes. 
         [0035]    In another preferred embodiment, the microarray of the present invention comprises between 701 and 818 nucleic acid sequences, wherein each of said sequences consists of a partial sequence of one of the genes present in the aforementioned group of 818 genes. 
         [0036]    In a particularly preferred embodiment, the microarray of the present invention comprises all of the 818 genes present in the aforementioned group of genes. 
         [0037]    In addition to the aforementioned at least two nucleic acids, the microarray may also comprise one or more control nucleic acid sequences. 
         [0038]    The substrate present in the microarray may consist of any suitable material or combination of materials. Preferably, however, the substrate is selected from the group consisting of ceramics, glasses, metal oxides, nitrocellulose and nylon. 
         [0039]    In a further aspect, the present invention also provides a kit comprising a solid-state nucleic acid microarray as defined and described herein together with an instruction sheet. 
         [0040]    Kits based on the other gene expression technologies used in the method of the invention (as described hereinabove) are also within the scope of the present invention. Thus, in one embodiment, the kit of the present invention comprises a set of relevant primers suitable for use in real time RT-PCR together with control solutions and an instruction sheet. In another embodiment, the kit comprises micro-well plates or similar vessels suitable for use in an ELISA assay, together with antibodies specific for isotopes present on the peptides and polypeptides expressed from the aforementioned defined set of genes, suitable reagents for signal detection and amplification and an instruction sheet. In yet another embodiment, the kit comprises antibodies specific for isotopes present on the peptides and polypeptides expressed from the aforementioned defined set of genes, together with reagents suitable for signal detection and amplification using standard immunochemical methods and an instruction sheet. 
         [0041]    All the above and other characteristics and advantages of the present invention will be further understood from the following illustrative and non-limitative examples of preferred embodiments thereof. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0042]      FIG. 1  illustrates the hierarchical clustering, Kaplan-Meier PFS analysis and gene clusters of Ewing sarcoma tumor samples. 
           [0000]    a, Illustration of the two sided 0  clusters dendogram, distinctly defining poor prognosis (1 st  8 columns from left to right) vs. good prognosis (6 right-most columns) groups of ES patients and the differentially expressed genes. Each column represents a patient and each row represents a gene.
 
b, Kaplan-Meier progression free survival analysis presents a significant correlation between poor prognosis vs. good prognosis patients, according to the microarray classification.
 
c, The 2 major gene clusters and the 6 subclusters, formed on the basis of the similarities of the 818 genes measured over the 14 tumor samples. The 2 gene clusters consist of differentially expressed genes: over-expressed in the poor prognosis group and down-regulated in the good prognosis group, and vice versa.
 
           [0043]      FIG. 2  graphically illustrates the correlation between expression of the cadherin-11 and the MTA1 genes by microarray analysis and by Real Time PCR. 
           [0000]    a, Expression mean log value of cadherin-11 in poor prognosis patients was significantly higher than the expression mean value in good prognosis patients by both analyses.
 
b, Gene expression pattern in the poor and good prognosis patients, was also significantly correlated by both analyses, for the MTA1 gene.
 
       
    
    
     DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS 
       [0044]    As mentioned, hereinabove, ES is the second most common primary malignant bone tumor in children and adolescents. In spite of advances in multimodal therapy, about 50% of patients eventually relapse, even after 5 years or more. Currently accepted clinical prognostic factors, fail to classify ES patients&#39; risk to relapse at diagnosis. 
         [0045]    The recent development of DNA microarrays provides an opportunity to take a genome-wide approach to extend biological insights into all aspects of the study of disease: pathogenesis, disease development, staging, prognosis and treatment response. Gene expression profiling using oligonucleotide high-density arrays has provided an additional tool for elucidating tumor biology as well as the potential for molecular classification of cancer. 
         [0046]    In the method of the present invention, oligonucleotide high-density array analysis of material derived from primary tumors is used to identify two distinct gene expression profiles distinguishing ES patients with poor and good prognosis. The results obtained with this method (including the results presented in the Example hereinbelow) indicate the existence of a specific gene expression signature of outcome in ES, already at diagnosis thereby providing a strategy, based upon gene expression patterns, for selecting patients who would benefit from risk adapted improved therapy. The gene expression patterns used in this strategy are based on data sets containing a minimum of 1 significant gene out of the 818 genes to a maximum of 818 genes. Intermediate-sized datasets containing up to 100 genes, 200 genes, 300 genes, 400 genes, 500 genes, 600 genes, 700 genes and 800 genes, may also be usefully defined and used in said selection and prognostic strategy. The present invention also encompasses nucleic acid bearing microarrays for use in the method disclosed herein, as well as kits containing all of the necessary materials and instructions for performing the abovementioned strategy or method, as disclosed and described in more detail hereinbelow. 
         [0047]    The details of the aforementioned group of 818 genes for use in accordance with a particularly preferred embodiment of the present invention are listed in Table 1: 
         [0000]    
       
         
               
               
               
             
           
               
                 TABLE 1 
               
               
                   
               
               
                 Gene 
                 Gene Name 
                 Gene Bank ID 
               
               
                   
               
             
             
               
                 FLII 
                 flightless I homolog ( Drosophila ) 
                 U80184 
               
               
                 PM5 
                 pM5 protein 
                 X57398 
               
               
                 PBEF 
                 pre-B-cell colony-enhancing factor 
                 U02020 
               
               
                 KIAA0892 
                 KIAA0892 protein 
                 AB020699 
               
               
                 HSD17B4 
                 hydroxysteroid (17-beta) dehydrogenase 4 
                 X87176 
               
               
                 IGKC 
                 immunoglobulin kappa constant 
                 X96754 
               
               
                 CDC14B 
                 CDC14 cell division cycle 14 homolog B ( S. cerevisiae ) 
                 AI739548 
               
               
                 SLC22A6 
                 “solute carrier family 22 (organic anion transporter), 
                 AB009698 
               
               
                   
                 member 6” 
               
               
                 NRTN 
                 neurturin 
                 U78110 
               
               
                 KIAA1096 
                 KIAA1096 protein 
                 AL096857 
               
               
                 IFRD1 
                 interferon-related developmental regulator 1 
                 AC005192 
               
               
                 KIAA0310 
                 KIAA0310 gene product 
                 AB002308 
               
               
                 ACAA1 
                 acetyl-Coenzyme A acyltransferase 1 (peroxisomal 3- 
                 X14813 
               
               
                   
                 oxoacyl-Coenzyme A thiolase) 
               
               
                 GRN 
                 granulin 
                 AF055008 
               
               
                 SH3BGR 
                 SH3 domain binding glutamic acid-rich protein 
                 X93498 
               
               
                 MJD 
                 “Machado-Joseph disease (spinocerebellar ataxia 3, 
                 U64820 
               
               
                   
                 olivopontocerebellar ataxia 3, autosomal dominant, 
               
               
                   
                 ataxin 3)” 
               
               
                 DKFZP564G2022 
                 DKFZP564G2022 protein 
                 AL049944 
               
               
                 EWSR1 
                 Ewing sarcoma breakpoint region 1 
                 X66899 
               
               
                 AHCYL1 
                 S-adenosylhomocysteine hydrolase-like 1 
                 AI800578 
               
               
                 KLRC3 
                 “killer cell lectin-like receptor subfamily C, member 3” 
                 AJ001685 
               
               
                 F2RL1 
                 coagulation factor II (thrombin) receptor-like 1 
                 U34038 
               
               
                 EIF4G1 
                 “eukaryotic translation initiation factor 4 gamma, 1” 
                 D12686 
               
               
                   
                   
                 D26561 
               
               
                 TP53BP2 
                 “tumor protein p53 binding protein, 2” 
                 U58334 
               
               
                 TP63 
                 tumor protein p63 
                 Y16961 
               
               
                 MAN2B1 
                 “mannosidase, alpha, class 2B, member 1” 
                 U60899 
               
               
                 BLCAP 
                 bladder cancer associated protein 
                 AL049288 
               
               
                 TAF6 
                 “TAF6 RNA polymerase II, TATA box binding protein 
                 L25444 
               
               
                   
                 (TBP)-associated factor, 80 kDa” 
               
               
                   
                   H. sapiens  hsr1 mRNA (partial) 
                 X66436 
               
               
                 STRN3 
                 “striatin, calmodulin binding protein 3” 
                 U17989 
               
               
                 KIAA0914 
                 KIAA0914 gene product 
                 AB020721 
               
               
                 SYNE-2 
                 synaptic nuclei expressed gene 2 
                 AL080133 
               
               
                 LLGL1 
                 lethal giant larvae homolog 1 ( Drosophila ) 
                 X86371 
               
               
                   
                   
                 M62302 
               
               
                 PSMD9 
                 “proteasome (prosome, macropain) 26S subunit, non- 
                 AB003177 
               
               
                   
                 ATpase, 9” 
               
               
                 IL4 
                 interleukin 4 
                 M13982 
               
               
                 EP400 
                 E1A binding protein p400 
                 AI143868 
               
               
                 DPAGT1 
                 dolichyl-phosphate (UDP-N-acetylglucosamine) N- 
                 Z82022 
               
               
                   
                 acetylglucosaminephosphotransferase 1 (GlcNAc-1-P 
               
               
                   
                 transferase) 
               
               
                 MKNK1 
                 MAP kinase-interacting serine/threonine kinase 1 
                 AB000409 
               
               
                 KIAA0356 
                 KIAA0356 gene product 
                 AB002354 
               
               
                 MET 
                 met proto-oncogene (hepatocyte growth factor receptor) 
                 J02958 
               
               
                 TPO 
                 thyroid peroxidase 
                 J02969 
               
               
                 EGFL5 
                 “EGF-like-domain, multiple 5” 
                 AB011542 
               
               
                 RRS1 
                 homolog of yeast ribosome biogenesis regulatory protein 
                 D25218 
               
               
                   
                 RRS1 
               
               
                 ARL1 
                 ADP-ribosylation factor-like 1 
                 L28997 
               
               
                 SDCBP 
                 syndecan binding protein (syntenin) 
                 AF000652 
               
               
                 B7 
                 B7 protein 
                 U72508 
               
               
                 SDBCAG84 
                 serologically defined breast cancer antigen 84 
                 AF091085 
               
               
                 REL 
                   Homo sapiens  mRNA; cDNA DKFZp434M162 (from 
                 W72239 
               
               
                   
                 clone DKFZp434M162) 
               
               
                   
                 v-rel reticuloendotheliosis viral oncogene homolog 
                 AA872560 
               
               
                   
                 (avian) 
               
               
                 SEMA3F 
                 “sema domain, immunoglobulin domain (Ig), short basic 
                 U38276 
               
               
                   
                 domain, secreted, (semaphorin) 3F” 
               
               
                   
                   
                 X71346 
               
               
                 KLK3 
                 “kallikrein 3, (prostate specific antigen)” 
                 X07730 
               
               
                 F7 
                 coagulation factor VII (serum prothrombin conversion 
                 M13232 
               
               
                   
                 accelerator) 
               
               
                 RBBP2 
                 retinoblastoma binding protein 2 
                 S66431 
               
               
                 KIAA0020 
                 KIAA0020 gene product 
                 D13645 
               
               
                 GRIN2A 
                 “glutamate receptor, ionotropic, N-methyl D-aspartate 
                 U09002 
               
               
                   
                 2A” 
               
               
                 GART 
                 “phosphoribosylglycinamide formyltransferase, 
                 X54199 
               
               
                   
                 phosphoribosylglycinamide synthetase, 
               
               
                   
                 phosphoribosylaminoimidazole synthetase” 
               
               
                 PSMB8 
                 “proteasome (prosome, macropain) subunit, beta type, 8 
                 X87344 
               
               
                   
                 (large multifunctional protease 7)” 
               
               
                 HTR2A 
                 5-hydroxytryptamine (serotonin) receptor 2A 
                 AA418537 
               
               
                 SURB7 
                 SRB7 suppressor of RNA polymerase B homolog (yeast) 
                 U52960 
               
               
                 MAP3K7IP2 
                 mitogen-activated protein kinase kinase kinase 7 
                 AB018276 
               
               
                   
                 interacting protein 2 
               
               
                 MGST3 
                 microsomal glutathione S-transferase 3 
                 AF026977 
               
               
                 PFDN1 
                 prefoldin 1 
                 D45333 
               
               
                 U2AF65 
                 U2 small nuclear ribonucleoprotein auxiliary factor 
                 AI762438 
               
               
                   
                 (65 kD) 
               
               
                 KRTHA2 
                 “keratin, hair, acidic, 2” 
                 X90761 
               
               
                 POU4F1 
                 “POU domain, class 4, transcription factor 1” 
                 L20433 
               
               
                 CTSO 
                 cathepsin O 
                 AI810485 
               
               
                 MAPK9 
                 mitogen-activated protein kinase 9 
                 U09759 
               
               
                 ISLR 
                 immunoglobulin superfamily containing leucine-rich 
                 AB003184 
               
               
                   
                 repeat 
               
               
                 DKFZP566B183 
                 DKFZP566B183 protein 
                 AL050272 
               
               
                 USP24 
                 ubiquitin specific protease 24 
                 AB028980 
               
               
                 PBX2 
                 pre-B-cell leukemia transcription factor 2 
                 X59842 
               
               
                 HT012 
                 uncharacterized hypothalamus protein HT012 
                 AI760162 
               
               
                   
                   
                 X17360 
               
               
                   
                   
                 HG162-HT3165 
               
               
                 HRIHFB2206 
                 HRIHFB2206 protein 
                 L10379 
               
               
                 SYBL1 
                 synaptobrevin-like 1 
                 X92396 
               
               
                 GRM4 
                 “glutamate receptor, metabotropic 4” 
                 X80818 
               
               
                 ATP5H 
                 “ATP synthase, H+ transporting, mitochondrial F0 
                 AF087135 
               
               
                   
                 complex, subunit d” 
               
               
                 MGC5149 
                 hypothetical protein MGC5149 
                 U79260 
               
               
                 C20orf188 
                 chromosome 20 open reading frame 188 
                 AF055022 
               
               
                 ZNF238 
                 zinc finger protein 238 
                 U38896 
               
               
                 KIAA1030 
                 KIAA1030 protein 
                 AB028953 
               
               
                 PLU-1 
                 putative DNA/chromatin binding motif 
                 AJ132440 
               
               
                 CCT8 
                 “chaperonin containing TCP1, subunit 8 (theta)” 
                 D13627 
               
               
                 XRCC2 
                 X-ray repair complementing defective repair in Chinese 
                 Y08837 
               
               
                   
                 hamster cells 2 
               
               
                 KIAA0170 
                 KIAA0170 gene product 
                 AL041663 
               
               
                 LPIN2 
                 lipin 2 
                 D87436 
               
               
                 SULT4A1 
                 “sulfotransferase family 4A, member 1” 
                 W25958 
               
               
                 CDX2 
                 caudal type homeo box transcription factor 2 
                 U51096 
               
               
                 CFDP1 
                 craniofacial development protein 1 
                 D85939 
               
               
                   
                   
                 HG1155-HT4822 
               
               
                 CDK2 
                 cyclin-dependent kinase 2 
                 M68520 
               
               
                 KIAA0737 
                 KIAA0737 gene product 
                 AF014837 
               
               
                 NTSR2 
                 neurotensin receptor 2 
                 Y10148 
               
               
                 PRSS15 
                 “protease, serine, 15” 
                 X76040 
               
               
                 UBE2M 
                 “ubiquitin-conjugating enzyme E2M (UBC12 homolog, 
                 AF075599 
               
               
                   
                 yeast)” 
               
               
                 NEUROD2 
                 neurogenic differentiation 2 
                 AB021742 
               
               
                 PCBP3 
                 poly(rC) binding protein 3 
                 AL046394 
               
               
                 CDK5 
                 cyclin-dependetent kinase 5 
                 L04658 
               
               
                 UBE3B 
                 ubiquitin protein ligase 
                 AL096740 
               
               
                 ALDH9A1 
                 “aldehyde dehydrogenase 9 family, member A1” 
                 U34252 
               
               
                 HCS 
                 cytochrome c 
                 D00265 
               
               
                 TUFM 
                 “Tu translation elongation factor, mitochondrial” 
                 S75463 
               
               
                 TFCP2 
                 transcription factor CP2 
                 U03494 
               
               
                 KIAA0963 
                 KIAA0963 protein 
                 AI760801 
               
               
                 SIAH1 
                 seven in absentia hamolog 1 ( Drosophila ) 
                 W26406 
               
               
                 CRHR2 
                 corticotropin releasing hormone receptor 2 
                 AF011406 
               
               
                 SLC7A11 
                 “solute carrier family 7, (cationic amino acid transporter, 
                 AB026891 
               
               
                   
                 y+ system) member 11” 
               
               
                 COL6A1 
                 “collagen, type VI, alpha 1” 
                 AA885106 
               
               
                 PTENP1 
                 “phosphatase and tensin homolog (mutated in multiple 
                 AF019083 
               
               
                   
                 advanced cancers 1), pseudogene 1” 
               
               
                 PDAP1 
                 PDGFA associated protein 1 
                 U41745 
               
               
                   
                   
                 U05681 
               
               
                 RAD50 
                 RAD50 homolog ( S. cerevisiae ) 
                 U63139 
               
               
                   
                   
                 M13970 
               
               
                 LRBA 
                 “LPS-responsive vesicle trafficking, beach and anchor 
                 M83822 
               
               
                   
                 containing” 
               
               
                 ARS2 
                 arsenate resistance protein ARS2 
                 AI972631 
               
               
                   
                   
                 AJ002428 
               
               
                 ANXA2P1 
                 annexin A2 pseudogene 1 
                 M62896 
               
               
                 ERCC2 
                 “excision repair cross-complementing rodent repair 
                 AA079018 
               
               
                   
                 deficiency, complementation group 2 (xeroderma 
               
               
                   
                 pigmentosum D)” 
               
               
                 ORC3L 
                 “origin recognition complex, subunit 3-like (yeast)” 
                 AL080116 
               
               
                 TNFRSF12 
                 “tumor necrosis factor receptor superfamily, member 12 
                 U83598 
               
               
                   
                 (translocating chain-association membrane protein)” 
               
               
                 COX6A1 
                 cytochrome c oxidase subunit VIa polypeptide 1 
                 AI540925 
               
               
                 PRL 
                 prolactin 
                 M29386 
               
               
                 PIM1 
                 pim-1 oncogene 
                 M54915 
               
               
                   
                   Homo sapiens  mRNA full length insert cDNA clone 
                 AL109702 
               
               
                   
                 EUROIMAGE 42138 
               
               
                 CCBP2 
                 chemokine binding protein 2 
                 U94888 
               
               
                 PTS 
                 6-pyruvoyltetrahydropterin synthase 
                 L76259 
               
               
                 GSTA4 
                 glutathione S-transferase A4 
                 AF025887 
               
               
                 PRSS25 
                 “protease, serine, 25” 
                 AF020760 
               
               
                 SEC14L1 
                 SEC14-like 1 ( S. cerevisiae ) 
                 D67029 
               
               
                 FGF18 
                 fibroblast growth factor 18 
                 AA022949 
               
               
                   
                   
                 U46194 
               
               
                 FLJ20580 
                 hypothetical protein FLJ20580 
                 AI862521 
               
               
                 DKFZP586B0923 
                 DKFZP586B0923 protein 
                 AL050190 
               
               
                   
                   Homo sapiens  mRNA; cDNA DKFZp434A012 (from 
                 AL096752 
               
               
                   
                 clone DKFZp434A012) 
               
               
                 PTK2B 
                 protein tyrosine kinase 2 beta 
                 U43522 
               
               
                 RNF13 
                 ring finger protein 13 
                 AF037204 
               
               
                 ATR 
                 ataxia telangiectasia and Rad3 related 
                 U49844 
               
               
                 USP19 
                 ubiquitin specific protease 19 
                 AB020698 
               
               
                 DDX21 
                 DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 21 
                 U41387 
               
               
                 STK3 
                 “serine/threonine kinase 3 (STE20 homolog, yeast)” 
                 U26424 
               
               
                 MAAT1 
                 melanoma-associated antigen recognised by cytotoxic T 
                 U19796 
               
               
                   
                 lymphocytes 
               
               
                   
                   
                 W28193 
               
               
                 TMEM1 
                 transmembrane protein 1 
                 AB001523 
               
               
                 MYB 
                 v-myb myeloblastosis viral oncogene homolog (avian) 
                 M13666 
               
               
                 RER1 
                 similar to  S. cerevisiae  RER1 
                 AW044624 
               
               
                 RBM9 
                 RNA binding motif protein 9 
                 AA402524 
               
               
                 DKFZP586A0522 
                 DKFZP586A0522 protein 
                 AL050159 
               
               
                 MVK 
                 mevalonate kinase (mevalonic aciduria) 
                 M88468 
               
               
                 CHIT1 
                 chitinase 1 (chitotriosidase) 
                 U29615 
               
               
                   
                 “ Homo sapiens  cDNA FLJ32313 fis, clone 
                 AI932613 
               
               
                   
                 PROST2003232, weakly similar to BETA- 
               
               
                   
                 GLUCURONIDASE PRECURSOR (EC 3.2.1.31)” 
               
               
                 KIAA1079 
                 KIAA1079 protein 
                 AI971726 
               
               
                 TCFL4 
                 transcription factor-like 4 
                 AW005997 
               
               
                 UBE2B 
                 ubiquitin-conjugating enzyme E2B (RAD6 homolog) 
                 M74525 
               
               
                 HR44 
                 Hr44 antigen 
                 X91103 
               
               
                 CDC5L 
                 CDC5 cell division cycle 5-like ( S. pombe ) 
                 AB007892 
               
               
                 EIF4G1 
                 “eukaryotic translation initiation factor 4 gamma, 1” 
                 AF104913 
               
               
                 GNB1 
                 “guanine nucleotide binding protein (G protein), beta 
                 X04526 
               
               
                   
                 polypeptide 1” 
               
               
                 NRG2 
                 neuregulin 2 
                 AA706226 
               
               
                 XPNPEP1 
                 “X-prolyl aminopeptidase (aminopeptidase P) 1, soluble” 
                 X95762 
               
               
                 ODC1 
                 ornithine decarboxylase 1 
                 X16277 
               
               
                 ALMS1 
                 Alstrom syndrome 1 
                 R40666 
               
               
                 VAPB 
                 VAMP (vesicle-associated membrane protein)- 
                 W27026 
               
               
                   
                 associated protein B and C 
               
               
                 UTRN 
                 utrophin (homologous to dystrophin) 
                 X69086 
               
               
                 GPR49 
                 G protein-coupled receptor 49 
                 AF062006 
               
               
                 PPP2R4 
                 “protein phosphatase 2A, regulatory subunit B′ (PR 53)” 
                 X73478 
               
               
                 RABGGTB 
                 “Rab geranylgeranyltransferase, beta subunit” 
                 X98001 
               
               
                 AP3S2 
                 “adaptor-related protein complex 3, sigma 2 subunit” 
                 X99459 
               
               
                 KIAA0171 
                 KIAA0171 gene product 
                 D79993 
               
               
                 ABCC8 
                 “ATP-binding cassette, sub-family C (CFTR/MRP), 
                 L78207 
               
               
                   
                 member 8” 
               
               
                 LOC51634 
                 CGI-79 protein 
                 AL050405 
               
               
                   
                   Homo sapiens  clone 24487 mRNA sequence 
                 AF070579 
               
               
                 SAH 
                 SA hypertension-associated homolog (rat) 
                 X80062 
               
               
                 TCF8 
                 transcription factor 8 (represses interleukin 2 expression) 
                 U19969 
               
               
                 ADCYAP1 
                 adenylate cyclase activating polypeptide 1 (pituitary) 
                 X60435 
               
               
                 DEK 
                 DEK oncogene (DNA binding) 
                 X64229 
               
               
                 DBP 
                 D site of albumin promoter (albumin D-box) binding 
                 U48213 
               
               
                   
                 protein 
               
               
                 ITGAE 
                 “integrin, alpha E (antigen CD103, human mucosal 
                 L25851 
               
               
                   
                 lymphocyte antigen 1; alpha polypeptide)” 
               
               
                 ABCF2 
                 “ATP-binding cassette, sub-family F (GCN20), member 
                 AJ005016 
               
               
                   
                 2” 
               
               
                 SC5DL 
                 “sterol-C5-desaturase (ERG3 delta-5-desaturase 
                 AB016247 
               
               
                   
                 homolog, fungal)-like” 
               
               
                   
                   
                 D50525 
               
               
                 LGALS9 
                 “lectin, galactoside-binding, soluble, 9 (galectin 9)” 
                 Z49107 
               
               
                 CUL1 
                 cullin 1 
                 U58087 
               
               
                 GYPE 
                 glycophorin E 
                 X53004 
               
               
                 DIAPH2 
                 diaphanous homolog 2 ( Drosophila ) 
                 Y15909 
               
               
                 PSR 
                 phosphatidylserine receptor 
                 AI950382 
               
               
                 LIPA 
                 “lipase A, lysosomal acid, cholesterol esterase (Wolman 
                 X76488 
               
               
                   
                 disease)” 
               
               
                 PSMD11 
                 “proteasome (prosome, macropain) 26S subunit, non- 
                 AB003102 
               
               
                   
                 ATPase, 11” 
               
               
                 PSMA3 
                 “proteasome (prosome, macropain) subunit, alpha type, 
                 D00762 
               
               
                   
                 3” 
               
               
                 VBP1 
                 von Hippel-Lindau binding protein 1 
                 U56833 
               
               
                 SIX6 
                 sine oculis homeobox homolog 6 ( Drosophila   
                 AJ011785 
               
               
                 RBL2 
                 retinoblastoma-like 2 (p130) 
                 X76061 
               
               
                 KCNAB1 
                 “potassium voltage-gated channel, shaker-related 
                 X83127 
               
               
                   
                 subfamily, beta member 1” 
               
               
                 EP300 
                 E1A binding protein p300 
                 U01877 
               
               
                 ABO 
                 “ABO blood group (transferase A, alpha 1-3-N- 
                 X84746 
               
               
                   
                 acetylgalactosaminyltransferase; transferase B, alpha 1- 
               
               
                   
                 3-galactosyltransferase)” 
               
               
                 GRIK5 
                 “glutamate receptor, ionotropic, kainate 5” 
                 AA977136 
               
               
                 ADPRTL1 
                 ADP-ribosyltransferase (NAD+; poly (ADP-ribose) 
                 AF057160 
               
               
                   
                 polymerase)-like 1 
               
               
                 HBXIP 
                 hepatitis B virus x interacting protein 
                 AF029890 
               
               
                 BHC80 
                 BRAF35/HDAC2 complex (80 kDa) 
                 W25985 
               
               
                 KIAA0436 
                 putative L-type neutral amino acid transporter 
                 AB007896 
               
               
                 MDH2 
                 “malate dehydrogenase 2, NAD (mitochondrial)” 
                 AF047470 
               
               
                 KIAA0630 
                 KIAA0630 protein 
                 AB014530 
               
               
                 IL1RL1 
                 interleukin 1 receptor-like 1 
                 D12763 
               
               
                 DMTF1 
                 cyclin D binding myb-like transcription factor 1 
                 AF052102 
               
               
                 MLH1 
                 “mutL homolog 1, colon cancer, nonpolyposis type 2 ( E. coli )” 
                 U07418 
               
               
                 GGTLA1 
                 gamma-glutamyltransferase-like activity 1 
                 M64099 
               
               
                 FHIT 
                 fragile histidine triad gene 
                 U46922 
               
               
                   
                 “ESTs, Weakly similar to I38724 mitochondrial 
                 AI052224 
               
               
                   
                 benzodiazepine receptor - human [ H. sapiens ]” 
               
               
                 ZNF278 
                 zinc finger protein 278 
                 AI352450 
               
               
                 HLCS 
                 holocarboxylase synthetase (biotin-[proprionyl- 
                 D87328 
               
               
                   
                 Coenzyme A-carboxylase (ATP-hydrolysing)] ligase) 
               
               
                 LOC57147 
                 hypothetical protein LOC57147 
                 W26641 
               
               
                 HTR4 
                 5-hydroxytryptamine (serotonin) receptor 4 
                 Y12505 
               
               
                 MORF 
                 monocytic leukemia zinc finger protein-related factor 
                 AB002381 
               
               
                 AANAT 
                 arylalkylamine N-acetyltransferase 
                 U40391 
               
               
                 MGP 
                 matrix Gla protein 
                 AI953789 
               
               
                   
                   
                 AB012229 
               
               
                 FLJ13052 
                 NAD kinase 
                 AL031282 
               
               
                 VAPB 
                 VAMP (vesicle-associated membrane protein)- 
                 W25933 
               
               
                   
                 associated protein B and C 
               
               
                 ENTPD1 
                 ectonucleoside triphosphate diphosphohydrolase 1 
                 AJ133133 
               
               
                 SDF2 
                 stromal cell-derived factor 2 
                 D50645 
               
               
                   
                   
                 U60269 
               
               
                 KIAA0907 
                 KIAA0907 protein 
                 AB020714 
               
               
                 SPRR2C 
                 small proline-rich protein 2C 
                 M21539 
               
               
                 DNAJB5 
                 “DnaJ (Hsp40) homolog, subfamily B, member 5” 
                 AF088982 
               
               
                 FMR2 
                 fragile X mental retardation 2 
                 U48436 
               
               
                 SLC7A8 
                 “solute carrier family 7 (cationic amino acid transporter, 
                 Y18483 
               
               
                   
                 y+ system), member 8” 
               
               
                 E2F5 
                 “E2F transcription factor 5, p130-binding” 
                 U31556 
               
               
                 LSM3 
                 Lsm3 protein 
                 N98670 
               
               
                 FLJ22678 
                 hypothetical protein FLJ22678 
                 AA165701 
               
               
                 PRKCABP 
                 “protein kinase C, alpha binding protein” 
                 AL049654 
               
               
                 DIP2 
                 disco-interacting protein 2 ( Drosophila ) homolog 
                 D80006 
               
               
                 CEP1 
                 centrosomal protein 1 
                 AF083322 
               
               
                 PAX6 
                 “paired box gene 6 (aniridia, keratitis)” 
                 M93650 
               
               
                 HLALS 
                 “major histocompatibility complex, class I-like sequence” 
                 AF031469 
               
               
                 MPV17 
                 “MpV17 transgene, murine homolog, glomerulosclerosis” 
                 X76538 
               
               
                   
                   
                 W29045 
               
               
                 KIAA0217 
                 KIAA0217 protein 
                 D86971 
               
               
                 RANBP7 
                 RAN binding protein 7 
                 AF098799 
               
               
                 UBE4A 
                 “ubiquitination factor E4A (UFD2 homolog, yeast)” 
                 D50916 
               
               
                 KIAA0337 
                 KIAA0337 gene product 
                 AB002335 
               
               
                 UPK1A 
                 uroplakin 1A 
                 AF085807 
               
               
                 ELAVL2 
                 “ELAV (embryonic lethal, abnormal vision,  Drosophila )- 
                 U29943 
               
               
                   
                 like 2 (HU antigen B)” 
               
               
                 PISD 
                 phosphatidylserine decarboxylase 
                 AL050371 
               
               
                 ZP3A 
                 zona pellucida glycoprotein 3A (sperm receptor) 
                 X56777 
               
               
                 HDAC3 
                 histone deacetylase 3 
                 U75697 
               
               
                 AD024 
                 AD024 protein 
                 W28610 
               
               
                 PFKFB2 
                 “6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2” 
                 AJ005577 
               
               
                 RRH 
                 retinal pigment epithelium-derived rhodopsin homolog 
                 AF012270 
               
               
                 IGHMBP2 
                 immunoglobulin mu binding protein 2 
                 L14754 
               
               
                 DSPG3 
                 dermatan sulfate proteogylcan 3 
                 U59111 
               
               
                   
                   Homo sapiens  mRNA; cDNA DKFZp434M245 (from 
                 W28661 
               
               
                   
                 clone DKFZp434M245) 
               
               
                 MAPK9 
                 mitogen-activated protein kinase 9 
                 U09759 
               
               
                   
                   
                 U64871 
               
               
                 AMMECR1 
                 “Alport syndrome, mental retardation, midface 
                 AJ007014 
               
               
                   
                 hypoplasia and elliptocytosis chromosomal region, gene 
               
               
                   
                 1” 
               
               
                 ATP6V1D 
                 “ATPase, H+ transporting, lysosomal 34 kDa, V1 subunit 
                 AA877795 
               
               
                   
                 D” 
               
               
                 ANP32A 
                 “acidic (leucine-rich) nuclear phosphoprotein 32 family, 
                 U73477 
               
               
                   
                 member A” 
               
               
                 PFAS 
                 phosphoribosylformylglycinamidine synthase (FGAR 
                 AB002359 
               
               
                   
                 amidotransferase) 
               
               
                 CPNE3 
                 copine III 
                 AB014536 
               
               
                 KIAA0410 
                 KIAA0410 gene product 
                 AB007870 
               
               
                 SET 
                 SET translocation (myeloid leukemia-associated) 
                 M93651 
               
               
                 CSTF2 
                 “cleavage stimulation factor, 3′ pre-RNA, subunit 2, 
                 M85085 
               
               
                   
                 64 kDa” 
               
               
                 ASNA1 
                 “arsA arsenite transporter, ATP-binding, homolog 1 
                 AF047469 
               
               
                   
                 (bacterial)” 
               
               
                 SLC2A1 
                 “solute carrier family 2 (facilitated glucose transporter), 
                 K03195 
               
               
                   
                 member 1” 
               
               
                 C8orf1 
                 chromosome 8 open reading frame 1 
                 AI738702 
               
               
                   
                   Homo sapiens  mRNA; cDNA DKFZp586K2322 (from 
                 AL080113 
               
               
                   
                 clone DKFZp586K2322) 
               
               
                 TM9SF1 
                 transmembrane 9 superfamily member 1 
                 U94831 
               
               
                 NDP 
                 Norrie disease (pseudoglioma) 
                 X65724 
               
               
                 YWHAE 
                 “tyrosine 3-monooxygenase/tryptophan 5- 
                 U54778 
               
               
                   
                 monooxygenase activation protein, epsilon polypeptide” 
               
               
                 KCNJ6 
                 “potassium inwardly-rectifying channel, subfamily J, 
                 U52153 
               
               
                   
                 member 6” 
               
               
                   
                   
                 X03453 
               
               
                 RFPL3 
                 ret finger protein-like 3 
                 AJ010232 
               
               
                 HCFC1 
                 host cell factor C1 (VP16-accessory protein) 
                 U52112 
               
               
                 SLC12A4 
                 “solute carrier family 12 (potassium/chloride 
                 AF054506 
               
               
                   
                 transporters), member 4” 
               
               
                 T 
                 “T, brachyury homolog (mouse)” 
                 AJ001699 
               
               
                 ZNF174 
                 zinc finger protein 174 
                 U31248 
               
               
                 TRAP100 
                 thyroid hormone receptor-associated protein (100 kDa) 
                 D50920 
               
               
                 HTR6 
                 5-hydroxytryptamine (serotonin) receptor 6 
                 L41147 
               
               
                 NASP 
                 nuclear autoantigenic sperm protein (histone-binding) 
                 M97856 
               
               
                 COMT 
                 catechol-O-methyltransferase 
                 M58525 
               
               
                 AXL 
                 AXL receptor tyrosine kinase 
                 M76125 
               
               
                 NME1 
                 “non-metastatic cells 1, protein (NM23A) expressed in” 
                 X73066 
               
               
                   
                   
                 M10098 
               
               
                 LOC51055 
                 unknown 
                 U88048 
               
               
                 CREM 
                 cAMP responsive element modulator 
                 S68271 
               
               
                 MEF-2 
                 myelin gene expression factor 2 
                 W28567 
               
               
                 PCBP1 
                 poly(rC) binding protein 1 
                 Z29505 
               
               
                 GNG5 
                 “guanine nucleotide binding protein (G protein), gamma 
                 AI541042 
               
               
                   
                 5” 
               
               
                 CNNM2 
                 cyclin M2 
                 AI827730 
               
               
                 NCSTN 
                 nicastrin 
                 D87442 
               
               
                 ICOS 
                 inducible T-cell co-stimulator 
                 AB023135 
               
               
                 TK2 
                 “thymidine kinase 2, mitochondrial” 
                 U80628 
               
               
                 LTK 
                 leukocyte tyrosine kinase 
                 X52213 
               
               
                 BRD2 
                 bromodomain containing 2 
                 D42040 
               
               
                 SMAP 
                 skeletal muscle abundant protein 
                 AF016270 
               
               
                   
                   Homo sapiens  retinoic acid-inducible endogenous 
                 M64936 
               
               
                   
                 retroviral DNA 
               
               
                 MYO1C 
                 myosin IC 
                 X98507 
               
               
                 IMAGE145052 
                 small acidic protein 
                 AI346580 
               
               
                   
                 “AML1 = AML1 {alternatively spliced, exons 5 and b} 
                 S76346 
               
               
                   
                 [human, mRNA Partial, 284 nt]” 
               
               
                 IKKE 
                 IKK-related kinase epsilon; inducible IkappaB kinase 
                 D63485 
               
               
                 LU 
                 Lutheran blood group (Auberger b antigen included) 
                 X80026 
               
               
                 KIAA0828 
                 KIAA0828 protein 
                 AB020635 
               
               
                 SLC30A3 
                 “solute carrier family 30 (zinc transporter), member 3” 
                 U76010 
               
               
                 IL13RA1 
                 “interleukin 13 receptor, alpha 1” 
                 Y10659 
               
               
                 C22orf4 
                 chromosome 22 open reading frame 4 
                 AL096779 
               
               
                 BCL11A 
                 B-cell CLL/lymphoma 11A (zinc finger protein) 
                 W27619 
               
               
                 HIPK3 
                 homeodomain interacting protein kinase 3 
                 AI523538 
               
               
                 ACVR1B 
                 “activin A receptor, type IB” 
                 Z22536 
               
               
                 UBA2 
                 SUMO-1 activating enzyme subunit 2 
                 AL041443 
               
               
                 THRA 
                 “thyroid hormone receptor, alpha (erythroblastic 
                 X55005 
               
               
                   
                 leukemia viral (v-erb-a) oncogene homolog, avian)” 
               
               
                 NCOA2 
                 nuclear receptor coactivator 2 
                 AI040324 
               
               
                 IRF2 
                 interferon regulatory factor 2 
                 X15949 
               
               
                   
                   
                 L38424 
               
               
                 GNAS 
                 GNAS complex locus 
                 X04409 
               
               
                 TM4SF6 
                 transmembrane 4 superfamily member 6 
                 AF043906 
               
               
                 ZK1 
                 Kruppel-type zinc finger (C2H2) 
                 AB011414 
               
               
                 ARPC5 
                 “actin related protein 2/3 complex, subunit 5, 16 kDa” 
                 AF006088 
               
               
                 PEX7 
                 peroxisomal biogenesis factor 7 
                 U88871 
               
               
                 FMR1 
                 fragile X mental retardation 1 
                 X69962 
               
               
                 ZP2 
                 zona pellucida glycoprotein 2 (sperm receptor) 
                 M90366 
               
               
                 OR7E126P 
                 “olfactory receptor, family 7, subfamily A, member 126 
                 AF065854 
               
               
                   
                 pseudogene” 
               
               
                 HSF4 
                 heat shock transcription factor 4 
                 D87673 
               
               
                   
                   
                 HG2702-HT2798 
               
               
                 UBE2G1 
                 “ubiquitin-conjugating enzyme E2G 1 (UBC7 homolog, 
                 D78514 
               
               
                   
                   C. elegans )” 
               
               
                 GRLF1 
                 glucocorticoid receptor DNA binding factor 1 
                 AI670100 
               
               
                 SSFA2 
                 sperm specific antigen 2 
                 M61199 
               
               
                 JIK 
                 STE20-like kinase 
                 W28742 
               
               
                 PPP3CC 
                 “protein phosphatase 3 (formerly 2B), catalytic subunit, 
                 AI762547 
               
               
                   
                 gamma isoform (calcineurin A gamma)” 
               
               
                 AHCYL1 
                 S-adenosylhomocysteine hydrolase-like 1 
                 AI800578 
               
               
                 PRCP 
                 prolylcarboxypeptidase (angiotensinase C) 
                 L13977 
               
               
                 NR2C1 
                 “nuclear receptor subfamily 2, group C, member 1” 
                 M29960 
               
               
                 FUS 
                 “fusion, derived from t(12; 16) malignant liposarcoma” 
                 S62140 
               
               
                 ZNF273 
                 zinc finger protein 273 
                 X78932 
               
               
                 MYST1 
                 MYST histone acetyltransferase 1 
                 AI417075 
               
               
                 NQO1 
                 “NAD(P)H dehydrogenase, quinone 1” 
                 M81600 
               
               
                 ADAM15 
                 a disintegrin and metalloproteinase domain 15 
                 U41767 
               
               
                   
                 (metargidin) 
               
               
                 CRYAB 
                 “crystallin, alpha B” 
                 AL038340 
               
               
                 DKFZp566D133 
                 DKFZp566D133 protein 
                 AL050050 
               
               
                 MAPRE1 
                 “microtubule-associated protein, RP/EB family, member 
                 U24166 
               
               
                   
                 1” 
               
               
                 TGFB1 
                 “transforming growth factor, beta 1 (Camurati- 
                 X02812 
               
               
                   
                 Engelmann disease)” 
               
               
                 ZNF189 
                 zinc finger protein 189 
                 AF025770 
               
               
                 ATP1B3 
                 “ATPase, Na+/K+ transporting, beta 3 polypeptide” 
                 U51478 
               
               
                 TG737 
                 “Probe hTg737 (polycystic kidney disease, autosomal 
                 U20362 
               
               
                   
                 recessive, in)” 
               
               
                 FST 
                 follistatin 
                 M19481 
               
               
                 DKFZP564O0423 
                 DKFZP564O0423 protein 
                 AL080120 
               
               
                 MAGEA4 
                 “melanoma antigen, family A, 4” 
                 U10688 
               
               
                 POU6F1 
                 “POU domain class 6, transcription factor 1” 
                 Z21966 
               
               
                 FLJ20986 
                 hypothetical protein FLJ20986 
                 Z24724 
               
               
                 LOC90586 
                 amine oxidase pseudogene 
                 AF047485 
               
               
                 MIPEP 
                 mitochondrial intermediate peptidase 
                 U80034 
               
               
                   
                   Homo sapiens  clone 24507 mRNA sequence 
                 AF052148 
               
               
                   
                   Homo sapiens  mRNA; cDNA DKFZp667O1814 (from 
                 W26677 
               
               
                   
                 clone DKFZp667O1814) 
               
               
                 HTR1E 
                 5-hydroxytryptamine (serotonin) receptor 1E 
                 M91467 
               
               
                 DKFZP564L0862 
                 DKFZP564L0862 protein 
                 AL080091 
               
               
                 HRB2 
                 HIV-1 rev binding protein 2 
                 U00943 
               
               
                 REA 
                 repressor of estrogen receptor activity 
                 U72511 
               
               
                 DOK1 
                 “docking protein 1, 62 kDa (downstream of tyrosine 
                 U70987 
               
               
                   
                 kinase 1)” 
               
               
                 KIAA0710 
                 KIAA0710 gene product 
                 AB014610 
               
               
                 PRNP 
                 “prion protein (p27-30) (Creutzfeld-Jakob disease, 
                 U29185 
               
               
                   
                 Gerstmann-Strausler-Scheinker syndrome, fatal familial 
               
               
                   
                 insomnia)” 
               
               
                 PTK7 
                 PTK7 protein tyrosine kinase 7 
                 U33635 
               
               
                 KIAA0426 
                 KIAA0426 gene product 
                 AB007886 
               
               
                   
                 “Phosphoglycerate kinase {alternatively spliced} [human, 
                 S81916 
               
               
                   
                 phosphoglycerate kinase deficient patient with episodes 
               
               
                   
                 of muscl, mRNA Partial Mutant, 307 nt]” 
               
               
                 NEDD4 
                 “neural precursor cell expressed, developmentally down- 
                 D42055 
               
               
                   
                 regulated 4” 
               
               
                 CSH2 
                 chorionic somatomammotropin hormone 2 
                 AA151971 
               
               
                 ARF4 
                 ADP-ribosylation factor 4 
                 M36341 
               
               
                 CD34 
                 CD34 antigen 
                 M81945 
               
               
                 KIAA0092 
                 KIAA0092 gene product 
                 D42054 
               
               
                 DKFZp434G2311 
                 hypothetical protein DKFZp434G2311 
                 W22289 
               
               
                 GYPB 
                 glycophorin B (includes Ss blood group) 
                 U05255 
               
               
                 TIC 
                 SEC7 homolog 
                 U63127 
               
               
                   
                   
                 X61072 
               
               
                 KIAA0552 
                 KIAA0552 gene product 
                 AB011124 
               
               
                 KIAA0970 
                 KIAA0970 protein 
                 AB023187 
               
               
                 SLC18A1 
                 “solute carrier family 18 (vesicular monoamine), member 
                 U39905 
               
               
                   
                 1” 
               
               
                   
                   
                 D86096 
               
               
                 S100A5 
                 S100 calcium binding protein A5 
                 Z18954 
               
               
                 EFNA3 
                 ephrin-A3 
                 U14187 
               
               
                 NM23-H6 
                 nucleoside diphosphate kinase type 6 (inhibitor of p53- 
                 AF051941 
               
               
                   
                 induced apoptosis-alpha) 
               
               
                 NXF1 
                 nuclear RNA export factor 1 
                 AJ132712 
               
               
                 SLC4A8 
                 “solute carrier family 4, sodium bicarbonate 
                 AB018282 
               
               
                   
                 cotransporter, member 8” 
               
               
                 IGHM 
                 immunoglobulin heavy constant mu 
                 AF015128 
               
               
                 EEF1A1 
                 eukaryotic translation elongation factor 1 alpha 1 
                 W28170 
               
               
                   
                   Homo sapiens  clone 24468 mRNA sequence 
                 AF070623 
               
               
                 USP9X 
                 “ubiquitin specific protease 9, X chromosome (fat facets- 
                 X98296 
               
               
                   
                 like  Drosophila )” 
               
               
                 DYRK2 
                 dual-specificity tyrosine-(Y)-phosphorylation regulated 
                 Y09216 
               
               
                   
                 kinase 2 
               
               
                 LBP 
                 lipopolysaccharide binding protein 
                 AF013512 
               
               
                 POH1 
                 26S proteasome-associated pad1 homolog 
                 U86782 
               
               
                 KIAA0211 
                 KIAA0214 gene product 
                 D86966 
               
               
                 PXR1 
                 peroxisome receptor 1 
                 Z48054 
               
               
                   
                   
                 HG2689-HT2785 
               
               
                 TAF4 
                 “TAF4 RNA polymerase II, TATA box binding protein 
                 U75308 
               
               
                   
                 (TBP)-associated factor, 135 kDa” 
               
               
                 ZNF313 
                 zinc finger protein 313 
                 AL031685 
               
               
                 PPAP2A 
                 phosphatidic acid phosphatase type 2A 
                 AF014402 
               
               
                 FLJ20323 
                 hypothetical protein FLJ20323 
                 AC004982 
               
               
                 TCP1 
                 t-complex 1 
                 X52882 
               
               
                 NR2F1 
                 “nuclear receptor subfamily 2, group F, member 1” 
                 X16155 
               
               
                 MAG 
                 myelin associated glycoprotein 
                 M29273 
               
               
                   
                   
                 J04423 
               
               
                 ELAC2 
                 elaC homolog 2 ( E. coli ) 
                 AA522537 
               
               
                 MAPKAPK2 
                 mitogen-activated protein kinase-activated protein kinase 2 
                 U12779 
               
               
                 SMAP 
                 skeletal muscle abundant protein 
                 X87613 
               
               
                 ZNF263 
                 zinc finger protein 263 
                 D88827 
               
               
                 DDX27 
                 DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 27 
                 W25911 
               
               
                 HSA6591 
                 nucleolar cysteine-rich protein 
                 AJ006591 
               
               
                 MAGOH 
                 “mago-nashi homolog, proliferation-associated 
                 AF035940 
               
               
                   
                 ( Drosophila )” 
               
               
                   
                   
                 Y16788 
               
               
                 KRT2A 
                 keratin 2A (epidermal ichthyosis bullosa of Siemens) 
                 AF019084 
               
               
                 RALY 
                 “RNA binding protein (autoantigenic, hnRNP-associated 
                 L38696 
               
               
                   
                 with lethal yellow)” 
               
               
                 C11orf9 
                 chromosome 11 open reading frame 9 
                 AB023171 
               
               
                 XPO1 
                 “exportin 1 (CRM1 homolog, yeast)” 
                 Y08614 
               
               
                 H2BFC 
                 “H2B histone family, member C” 
                 AL009179 
               
               
                 SETDB1 
                 “SET domain, bifurcated 1” 
                 D31891 
               
               
                 SEC63L 
                 SEC63 protein 
                 AJ011779 
               
               
                 MGC8721 
                 hypothetical protein MGC8721 
                 W26659 
               
               
                 RPP40 
                 “ribonuclease P, 40 kD subunit” 
                 U94317 
               
               
                 GAPD 
                 glyceraldehyde-3-phosphate dehydrogenase 
                 M33197 
               
               
                 KIAA0467 
                 KIAA0467 protein 
                 AB007936 
               
               
                 KCNMB1 
                 “potassium large conductance calcium-activated 
                 U25138 
               
               
                   
                 channel, subfamily M, beta member 1” 
               
               
                 PML 
                 promyelocytic leukemia 
                 M79463 
               
               
                 B2M 
                 beta-2-microglobulin 
                 S82297 
               
               
                 UROS 
                 uroporphyrinogen III synthase (congenital erythropoietic 
                 J03824 
               
               
                   
                 porphyria) 
               
               
                 PDE4A 
                 “phosphodiesterase 4A, cAMP-specific 
                 L20965 
               
               
                   
                 (phosphodiesterase E2 dunce homolog,  Drosophila )” 
               
               
                   
                   
                 M59830 
               
               
                 NUP155 
                 nucleoporin 155 kDa 
                 AB018334 
               
               
                 HRMT1L1 
                 HMT1 hnRNP methyltransferase-like 1 ( S. cerevisiae ) 
                 X99209 
               
               
                 BTN3A2 
                 “butyrophilin, subfamily 3, member A2” 
                 U97502 
               
               
                 TRAP100 
                 thyroid hormone receptor-associated protein (100 kDa) 
                 W29091 
               
               
                 PRKCD 
                 “protein kinase C, delta” 
                 D10495 
               
               
                 OAZ2 
                 ornithine decarboxylase antizyme 2 
                 AF057297 
               
               
                 ADRBK1 
                 “adrenergic, beta, receptor kinase 1” 
                 U08438 
               
               
                   
                 “ Homo sapiens  cDNA FLJ30824 fis, clone 
                 H12054 
               
               
                   
                 FEBRA2001698” 
               
               
                 GTF2H4 
                 “general transcription factor IIH, polypeptide 4, 52 kDa” 
                 Y07595 
               
               
                 LGALS9 
                 “lectin, galactoside-binding, soluble, 9 (galectin 9)” 
                 AB006782 
               
               
                 ACTB 
                 “actin, beta” 
                 X00351 
               
               
                 TMSB4Y 
                 “thymosin, beta 4, Y chromosome” 
                 AF000989 
               
               
                 GTF3C2 
                 “general transcription factor IIIC, polypeptide 2, beta 
                 D13636 
               
               
                   
                 110 kDa” 
               
               
                 C9orf3 
                 chromosome 9 open reading frame 3 
                 AF043897 
               
               
                 NSEP1 
                 nuclease sensitive element binding protein 1 
                 M85234 
               
               
                 TNP1 
                 transition protein 1 (during histone to protamine 
                 X07948 
               
               
                   
                 replacement) 
               
               
                   
                   
                 D10995 
               
               
                 HEXA 
                 hexosaminidase A (alpha polypeptide) 
                 M16424 
               
               
                 CCNF 
                 cyclin F 
                 Z36714 
               
               
                   
                   
                 AL034450 
               
               
                 SIP 
                 Siah-interacting protein 
                 AL035305 
               
               
                   
                   
                 X81832 
               
               
                 HLA-F 
                 “major histocompatibility complex, class I, F” 
                 AL022723 
               
               
                 DKFZP434D1335 
                 DKFZP434D1335 protein 
                 AI920820 
               
               
                 RNASEH1 
                 ribonuclease H1 
                 AF039652 
               
               
                   
                 “ Homo sapiens  cDNA: FLJ23482 fis, clone KAIA03142” 
                 U55980 
               
               
                 KIAA0877 
                 KIAA0877 protein 
                 AB020684 
               
               
                 CLTB 
                 “clathrin, light polypeptide (Lcb)” 
                 X81637 
               
               
                 HSPA8 
                 heat shock 70 kDa protein 8 
                 Y00371 
               
               
                 CTNNA1 
                 “catenin (cadherin-associated protein), alpha 1 (102 kDa” 
                 U03100 
               
               
                   
                   
                 W27906 
               
               
                 EIF4A2 
                 “eukaryotic translation initiation factor 4A, isoform 2” 
                 D30655 
               
               
                 H2BFN 
                 “H2B histone family, member N” 
                 Z98744 
               
               
                 KIAA0514 
                 KIAA0514 gene product 
                 AB011086 
               
               
                 PRPS1 
                 phosphoribosyl pyrophosphate synthetase 1 
                 D00860 
               
               
                 PAX8 
                 paired box gene 8 
                 X69699 
               
               
                   
                   
                 U10689 
               
               
                 B4GALT4 
                 “UDP-Gal:betaGlcNAc beta 1,4-galactosyltransferase, 
                 AF038662 
               
               
                   
                 polypeptide 4” 
               
               
                   
                   Homo sapiens  clone 23821 mRNA sequence 
                 AF038194 
               
               
                 PAFAH1B1 
                 “platelet-activating factor acetylhydrolase, isoform Ib, 
                 L13385 
               
               
                   
                 alpha subunit 45 kDa” 
               
               
                 IFNA10 
                 “interferon, alpha 10” 
                 V00551 
               
               
                 ABCB10 
                 “ATP-binding cassette, sub-family B (MDR/TAP), 
                 U18237 
               
               
                   
                 member 10” 
               
               
                 CASP10 
                 “caspase 10, apoptosis-related cysteine protease” 
                 U60519 
               
               
                 PFKM 
                 “phosphofructokinase, muscle” 
                 U24183 
               
               
                 RCN2 
                 “reticulocalbin 2, EF-hand calcium binding domain” 
                 X78669 
               
               
                 PPP3CB 
                 “protein phosphatase 3 (formerly 2B), catalytic subunit, 
                 M29550 
               
               
                   
                 beta isoform (calcineurin A beta)” 
               
               
                 H6PD 
                 hexose-6-phosphate dehydrogenase (glucose 1- 
                 AJ012590 
               
               
                   
                 dehydrogenase) 
               
               
                 PTPRA 
                 “protein tyrosine phosphatase, receptor type, A” 
                 M34668 
               
               
                 FUT7 
                 “fucosyltransferase 7 (alpha (1,3) fucosyltransferase)” 
                 AB012668 
               
               
                 PFKP 
                 “phosphofructokinase, platelet” 
                 D25328 
               
               
                 MAGEA9 
                 “melanoma antigen, family A, 9” 
                 U10694 
               
               
                 SDFR1 
                 stromal cell derived factor receptor 1 
                 AF035287 
               
               
                 CAV2 
                 caveolin 2 
                 AF035752 
               
               
                 ERCC5 
                 “excision repair cross-complementing rodent repair 
                 L20046 
               
               
                   
                 deficiency, complementation group 5 (xeroderma 
               
               
                   
                 pigmentosum, complementation group G (Cockayne 
               
               
                   
                 syndrome))” 
               
               
                 MLN 
                 motilin 
                 X15393 
               
               
                 PTK2 
                 PTK2 protein tyrosine kinase 2 
                 L13616 
               
               
                 P84 
                 nuclear matrix protein p84 
                 L36529 
               
               
                 OS4 
                 conserved gene amplified in osteosarcoma 
                 AF000152 
               
               
                 ITPR2 
                 “inositol 1,4,5-triphosphate receptor, type 2” 
                 D26350 
               
               
                 POU6F1 
                 “POU domain, class 6, transcription factor 1” 
                 Z21966 
               
               
                 GATA2 
                 GATA binding protein 2 
                 M77810 
               
               
                 SFRS7 
                 “splicing factor, arginine/serine-rich 7, 35 kDa” 
                 L41887 
               
               
                 FBXO21 
                 F-box only protein 21 
                 AB020682 
               
               
                 AGM1 
                 N-acetylglucosamine-phosphate mutase 
                 AA001791 
               
               
                 UGT2B15 
                 “UDP glycosyltransferase 2 family, polypeptide B15” 
                 U06641 
               
               
                 SGNE1 
                 “secretory granule, neuroendocrine protein 1 (7B2 
                 Y00757 
               
               
                   
                 protein)” 
               
               
                 CHP 
                 calcium binding protein P22 
                 U61538 
               
               
                 PDCD10 
                 programmed cell death 10 
                 AF022385 
               
               
                 FLJ21432 
                 hypothetical protein FLJ21432 
                 W26655 
               
               
                 KIAA0692 
                 KIAA0692 protein 
                 AI924382 
               
               
                 HNRPH3 
                 heterogeneous nuclear ribonucleoprotein H3 (2H9) 
                 AF052131 
               
               
                 OCRL 
                 oculocerebrorenal syndrome of Lowe 
                 U57627 
               
               
                 ESR2 
                 estrogen receptor 2 (ER beta) 
                 X99101 
               
               
                   
                   
                 HG1111-HT1111 
               
               
                   
                   Homo sapiens  mRNA; cDNA DKFZp586I1319 (from 
                 AL050106 
               
               
                   
                 clone DKFZp586I1319) 
               
               
                 SIM2 
                 single-minded homolog 2 ( Drosophila ) 
                 U80457 
               
               
                 DCTN1 
                 “dynactin 1 (p150, glued homolog,  Drosophila )” 
                 AF086947 
               
               
                 MGC9651 
                 hypothetical protein MGC9651 
                 W21884 
               
               
                 SFRS3 
                 “splicing factor, arginine/serine-rich 3” 
                 AF038250 
               
               
                 ZNF10 
                 zinc finger protein 10 (KOX 1) 
                 X52332 
               
               
                 AP2A2 
                 “adaptor-related protein complex 2, alpha 2 subunit” 
                 AB020706 
               
               
                 FLJ10618 
                 hypothetical protein FLJ10618 
                 AL049246 
               
               
                 TTTY15 
                 “testis-specific transcript, Y-linked 15” 
                 AL080135 
               
               
                 ID1 
                 “inhibitor of DNA binding 1, dominant negative helix-loop- 
                 X77956 
               
               
                   
                 helix protein” 
               
               
                 DAG1 
                 dystroglycan 1 (dystrophin-associated glycoprotein 1) 
                 L19711 
               
               
                 ZNF175 
                 zinc finger protein 175 
                 D50419 
               
               
                   
                   
                 W26472 
               
               
                 RAB2 
                 “RAB2, member RAS oncogene family” 
                 M28213 
               
               
                 ENPP4 
                 ectonucleotide pyrophosphatase/phosphodiesterase 4 
                 AB020686 
               
               
                   
                 (putative function) 
               
               
                 RHBDL 
                 “rhomboid, veinlet-like 1 ( Drosophila )” 
                 Y17108 
               
               
                 KIAA0648 
                 KIAA0648 protein 
                 AB014548 
               
               
                 UCHL3 
                 ubiquitin carboxyl-terminal esterase L3 (ubiquitin 
                 AA746355 
               
               
                   
                 thiolesterase) 
               
               
                 LOC51035 
                 ORF 
                 M68864 
               
               
                 ITGB2 
                 “integrin, beta 2 (antigen CD18 (p95), lymphocyte 
                 M15395 
               
               
                   
                 function-associated antigen 1; macrophage antigen 1 
               
               
                   
                 (mac-1) beta subunit)” 
               
               
                 PPP2R5C 
                 “protein phosphatase 2, regulatory subunit B (B56), 
                 Z69030 
               
               
                   
                 gamma isoform” 
               
               
                 MIR16 
                 membrane interacting protein of RGS16 
                 AC003108 
               
               
                 HSPCB 
                 “heat shock 90 kDa protein 1, beta” 
                 M16660 
               
               
                 ATP6V1A1 
                 “ATPase, H+ transporting, lysosomal 70 kDa, V1 subunit 
                 AA056747 
               
               
                   
                 A, isoform 1” 
               
               
                 CETN3 
                 “centrin, EF-hand protein, 3 (CDC31 homolog, yeast)” 
                 AI056696 
               
               
                 PRDX3 
                 peroxiredoxin 3 
                 D49396 
               
               
                 LOC129080 
                 putative emu1 
                 AL031186 
               
               
                 P2RX5 
                 “purinergic receptor P2X, ligand-gated ion channel, 5” 
                 U49395 
               
               
                 HUMPPA 
                 paraneoplastic antigen 
                 L02867 
               
               
                   
                   
                 HG2530-HT2626 
               
               
                 SCAP 
                 SREBP CLEAVAGE-ACTIVATING PROTEIN 
                 D83782 
               
               
                 MD-1 
                 “MD-1, RP105-associated” 
                 AB020499 
               
               
                 CDC6 
                 CDC6 cell division cycle 6 homolog ( S. cerevisiae ) 
                 U77949 
               
               
                 BRAP 
                 BRCA1 associated protein 
                 AL042733 
               
               
                 CAMK2G 
                 calcium/calmodulin-dependent protein kinase (CaM 
                 U66063 
               
               
                   
                 kinase) II gamma 
               
               
                 MLCB 
                 “myosin, light polypeptide, regulatory, non-sarcomeric 
                 X54304 
               
               
                   
                 (20 kD)” 
               
               
                 OPA1 
                 optic atrophy 1 (autosomal dominant) 
                 AB011139 
               
               
                 HSPC111 
                 hypothetical protein HSPC111 
                 AI553745 
               
               
                 STK39 
                 “serine threonine kinase 39 (STE20/SPS1 homolog, 
                 AF099989 
               
               
                   
                 yeast)” 
               
               
                 YME1L1 
                 YME1-like 1 ( S. cerevisiae ) 
                 AJ132637 
               
               
                 H1F2 
                 “H1 histone family, member 2” 
                 AI189287 
               
               
                 MLANA 
                 melan-A 
                 U06452 
               
               
                 PSMD9 
                 “proteasome (prosome, macropain) 26S subunit, non- 
                 AI347155 
               
               
                   
                 ATPase, 9” 
               
               
                 LARGE 
                 like-glycosyltransferase 
                 AJ007583 
               
               
                 CREB3 
                 cAMP responsive element binding protein 3 (luman) 
                 U88528 
               
               
                 MRPS14 
                 mitochondrial ribosomal protein S14 
                 AL049705 
               
               
                 TM4SF5 
                 transmembrane 4 superfamily member 5 
                 AF027204 
               
               
                 SIT 
                 SHP2 interacting transmembrane adaptor 
                 AJ010059 
               
               
                   
                   
                 Z48950 
               
               
                 EPB49 
                 erythrocyte membrane protein band 4.9 (dematin) 
                 U28389 
               
               
                 TCN2 
                 transcobalamin II; macrocytic anemia 
                 L02648 
               
               
                 OIP2 
                 Opa-Interacting protein 2 
                 AL050353 
               
               
                 ALAS2 
                 “aminolevulinate, delta-, synthase 2 
                 X60364 
               
               
                   
                 (sideroblastic/hypochromic anemia)” 
               
               
                 CHC1 
                 chromosome condensation 1 
                 X12654 
               
               
                 GMPS 
                 guanine monphosphate synthetase 
                 U10860 
               
               
                 SLC25A14 
                 “solute carrier family 25 (mitochondrial carrier, brain), 
                 AF078544 
               
               
                   
                 member 14” 
               
               
                 HNRPM 
                 heterogeneous nuclear ribonucleoprotein M 
                 L03532 
               
               
                 PDZ-GEF1 
                 PDZ domain containing guanine nucleotide exchange 
                 AB002311 
               
               
                   
                 factor(GEF)1 
               
               
                 UBE2N 
                 “ubiquitin-conjugating enzyme E2N (UBC13 homolog, 
                 D83004 
               
               
                   
                 yeast)” 
               
               
                   
                 “ESTs, Moderately similar to hypothetical protein 
                 W28230 
               
               
                   
                 FLJ20489 [ Homo sapiens ] [ H. sapiens ]” 
               
               
                 NEDD5 
                 “neural precursor cell expressed, developmentally down- 
                 M11717 
               
               
                   
                 regulated 5” 
                 D63878 
               
               
                   
                   
                 J04423 
               
               
                 CDH2 
                 “cadherin 2, type 1, N-cadherin (neuronal)” 
                 M34064 
               
               
                 PP35 
                 protein similar to  E. coli  yhdg and  R. capsulatus  nifR3 
                 U62767 
               
               
                   
                   Homo sapiens  mRNA; cDNA DKFZp686N1377 (from 
                 S63912 
               
               
                   
                 clone DKFZp686N1377) 
               
               
                   
                 “ Homo sapiens  cDNA FLJ13555 fis, clone 
                 AL080210 
               
               
                   
                 PLACE1007677” 
               
               
                   
                   
                 M33764 
               
               
                 RELN 
                 reelin 
                 U79716 
               
               
                 PPP1R12A 
                 “protein phosphatase 1, regulatory (inhibitor) subunit 
                 D87930 
               
               
                   
                 12A” 
               
               
                 SLC9A6 
                 “solute carrier family 9 (sodium/hydrogen exchanger), 
                 AF030409 
               
               
                   
                 isoform 6” 
               
               
                 NRXN1 
                 neurexin 1 
                 AB011150 
               
               
                 76P 
                 gamma tubulin ring complex protein (76p gene) 
                 W28255 
               
               
                 DKFZp564B0769 
                 SR rich protein 
                 AL080186 
               
               
                 ADPRT 
                 ADP-ribosyltransferase (NAD+; poly (ADP-ribose) 
                 J03473 
               
               
                   
                 polymerase) 
               
               
                 SRPX 
                 “sushi-repeat-containing protein, X chromosome” 
                 U61374 
               
               
                 SAS10 
                 disrupter of silencing 10 
                 AI126004 
               
               
                 GNAS 
                 GNAS complex locus 
                 X04409 
               
               
                   
                   
                 X57152 
               
               
                 MID2 
                 midline 2 
                 AL034399 
               
               
                 U5-100K 
                 “prp28, U5 snRNP 100 kd protein” 
                 AF026402 
               
               
                 PTPRD 
                 “protein tyrosine phosphatase, receptor type, D” 
                 AA843737 
               
               
                 SPTB 
                 “spectrin, beta, erythrocytic (includes spherocytosis, 
                 J05500 
               
               
                   
                 clinical type I)” 
               
               
                 CDK6 
                 cyclin-dependent kinase 6 
                 AI738463 
               
               
                 DPYSL4 
                 dihydropyrimidinase-like 4 
                 AB006713 
               
               
                 DKFZP566F0546 
                 DKFZP566F0546 protein 
                 AI671905 
               
               
                 CCT2 
                 “chaperonin containing TCP1, subunit 2 (beta)” 
                 AF026166 
               
               
                 PROL2 
                 proline rich 2 
                 U03105 
               
               
                   
                   
                 D00591 
               
               
                   
                   
                 M13929 
               
               
                 DR1 
                 “down-regulator of transcription 1, TBP-binding (negative 
                 M97388 
               
               
                   
                 cofactor 2)” 
               
               
                   
                   
                 L00049 
               
               
                 MTHFR 
                 “5,10-methylenetetrahydrofolate reductase (NADPH)” 
                 AJ237672 
               
               
                 SIMRP7 
                 multidrug resistance-associated protein 7 
                 AI004207 
               
               
                 CDH11 
                 “cadherin 11, type 2, OB-cadherin (osteoblast)” 
                 D21255 
               
               
                 FLJ11198 
                 hypothetical protein FLJ11198 
                 U66685 
               
               
                 ATRX 
                 “alpha thalassemia/mental retardation syndrome X-linked 
                 U72936 
               
               
                   
                 (RAD54 homolog,  S. cerevisiae )” 
               
               
                 BRCA1 
                 “breast cancer 1, early onset” 
                 U64805 
               
               
                 MLLT4 
                 “myeloid/lymphoid or mixed-lineage leukemia (trithorax 
                 AB011399 
               
               
                   
                 homolog,  Drosophila ); translocated to, 4” 
               
               
                 COX11 
                 “COX11 homolog, cytochrome c oxidase assembly 
                 U79270 
               
               
                   
                 protein (yeast)” 
               
               
                 TCEA1 
                 “transcrption elongation factor A (SII), 1” 
                 M81601 
               
               
                 TEGT 
                 testis enhanced gene transcript (BAX inhibitor 1) 
                 X75861 
               
               
                 RPL9 
                 ribosomal protein L9 
                 U09953 
               
               
                 CDK5R1 
                 “cyclin-dependent kinase 5, regulatory subunit 1 (p35)” 
                 X80343 
               
               
                   
                   
                 HG4518-HT4921 
               
               
                 SOS2 
                 son of sevenless homolog 2 ( Drosophila ) 
                 L13858 
               
               
                 EPHB2 
                 EphB2 
                 AF025304 
               
               
                   
                   
                 Z97054 
               
               
                 KIAA0185 
                 KIAA0185 protein 
                 D80007 
               
               
                 MYC 
                 v-myc myelocomatosis viral oncogene homolog (avian) 
                 V00568 
               
               
                 KCNK3 
                 “potassium channel, subfamily K, member 3” 
                 AF006823 
               
               
                 HSPA9B 
                 heat shock 70 kDa protein 9B (mortalin-2) 
                 L15189 
               
               
                 AIF1 
                 allograft inflammatory factor 1 
                 Y14768 
               
               
                 PMS2L6 
                 postmeiotic segregation increased 2-like 6 
                 AI341574 
               
               
                 DMWD 
                 dystrophia myotonica-containing WD repeat motif 
                 L19267 
               
               
                 GMPR 
                 guanosine monophosphate reductase 
                 M24470 
               
               
                 RTP801 
                 HIF-1 responsive RTP801 
                 M10098 
               
               
                 MMP11 
                 matrix metalloproteinase 11 (stromelysin 3) 
                 AA522530 
               
               
                   
                   
                 X57766 
               
               
                 KIAA1067 
                 KIAA1067 protein 
                 AB028990 
               
               
                 ADAM19 
                 a disintegrin and metalloproteinase domain 19 (meltrin 
                 AL049415 
               
               
                   
                 beta) 
               
               
                   
                   Homo sapiens  mRNA; cDNA DKFZp586F2224 (from 
                 AI655015 
               
               
                   
                 clone DKFZp586F2224) 
               
               
                 C1orf16 
                 chromosome 1 open reading frame 16 
                 D87437 
               
               
                 GP1BA 
                 “glycoprotein Ib (platelet), alpha polypeptide” 
                 J02940 
               
               
                 SDHB 
                 “succinate dehydrogenase complex, subunit B, iron 
                 U17886 
               
               
                   
                 sulfur (Ip)” 
               
               
                 NTRK2 
                 “neurotrophic tyrosine kinase, receptor, type 2” 
                 U12140 
               
               
                 KIAA0110 
                 gene predicted from cDNA with a complete coding 
                 D14811 
               
               
                   
                 sequence 
               
               
                 MAP3K7 
                 mitgen-activated protein kinase kinase kinase 7 
                 AB009356 
               
               
                 MGC5466 
                 hypothetical protein MGC5466 
                 U90904 
               
               
                 PPM1A 
                 “protein phosphatase 1A (formerly 2C), magnesium- 
                 S87759 
               
               
                   
                 dependent, alpha isoform” 
               
               
                   
                   
                 K01383 
               
               
                 KIAA0677 
                 KIAA0677 gene product 
                 AB014577 
               
               
                 HNRPA2B1 
                 heterogeneous nuclear ribonucleoprotein A2/B1 
                 M29065 
               
               
                 DKFZP434J046 
                 DKFZP434J046 protein 
                 AC004144 
               
               
                 MAN1A1 
                 “mannosidase, alpha, class 1A, member 1” 
                 X74837 
               
               
                 KIAA0455 
                 KIAA0455 gene product 
                 AB007924 
               
               
                 NUP160 
                 nucleoporin 160 kDa 
                 D83781 
               
               
                 NMT1 
                 N-myristoyltransferase 1 
                 M86707 
               
               
                 PIP5K1C 
                 “phosphatidylinositol-4-phosphate 5-kinase, type I, 
                 AB011161 
               
               
                   
                 gamma” 
               
               
                 GTF2H3 
                 “general transcription factor IIH, polypeptide 3, 34 kDa” 
                 Z30093 
               
               
                 DCN 
                 decorin 
                 M14219 
               
               
                   
                 “Human small proline rich protein (sprII) mRNA, clone 
                 M21302 
               
               
                   
                 174N” 
               
               
                 POLR2B 
                 “polymerase (RNA) II (DNA directed) polypetide B, 
                 X63563 
               
               
                   
                 140 kDa” 
               
               
                   
                   
                 J04988 
               
               
                 AHSG 
                 alpha-2-HS-glycoprotein 
                 M16961 
               
               
                 STAM 
                 signal transducing adaptor molecule (SH3 domain and 
                 U43899 
               
               
                   
                 ITAM motif) 1 
               
               
                 SCAM-1 
                 vinexin beta (SH3-containing adaptor molecule-1) 
                 AF037261 
               
               
                 RAF1 
                 v-raf-1 murine leukemia viral oncogene homolog 1 
                 X06409 
               
               
                 KIAA0964 
                 KIAA0964 protein 
                 AB023181 
               
               
                 SPARCL1 
                 “SPARC-like 1 (mast9, hevin)” 
                 X86693 
               
               
                 PGRMC1 
                 progesterone receptor membrane component 1 
                 Y12711 
               
               
                 COPS5 
                 COP9 constitutive photomorphogenic homolog subunit 5 
                 U65928 
               
               
                   
                 ( Arabidopsis ) 
               
               
                 MGC2650 
                 hypothetical protein MGC2650 
                 AI885381 
               
               
                 CYP11A 
                 “cytochrome P450, subfamily XIA (cholesterol side chain 
                 M14565 
               
               
                   
                 cleavage)” 
               
               
                 CPB2 
                 “carboxypeptidase B2 (plasma, carboxypeptidase U)” 
                 M75106 
               
               
                 NRG1 
                 neuregulin 1 
                 L41827 
               
               
                 GTF2F2 
                 “general transcription factor IIF, polypeptide 2, 30 kDa” 
                 X16901 
               
               
                 UCP2 
                 “uncoupling protein 2 (mitochondrial, proton carrier)” 
                 U94592 
               
               
                 BM036 
                 uncharacterized bone marrow protein BM036 
                 AI057607 
               
               
                 HLA-G 
                 “HLA-G histocompatibility antigen, class I, G” 
                 M90683 
               
               
                 SS18L1 
                 synovial sarcoma translocation gene on chromosome 
                 AB014593 
               
               
                   
                 18-like 1 
               
               
                 DKFZP547E1010 
                 DKFZP547E1010 protein 
                 AL050260 
               
               
                 PARG 
                 poly (ADP-ribose) glycohydrolase 
                 AF005043 
               
               
                 RPS15A 
                 ribosomal protein S15a 
                 W52024 
               
               
                 CREBL2 
                 cAMP responsive element binding protein-like 2 
                 AF039081 
               
               
                 HSD17B3 
                 hydroxysteroid (17-beta) dehydrogenase 3 
                 U05659 
               
               
                   
                   Homo sapiens  clone 23718 mRNA sequence 
                 AF052138 
               
               
                   
                   
                 HG2465-HT4871 
               
               
                 IDI1 
                 isopentenyl-diphosphate delta isomerase 
                 X17025 
               
               
                 CBX3 
                 “chromobox homolog 3 (HP1 gamma homolog, 
                 AA648295 
               
               
                   
                   Drosophila )” 
               
               
                 PAI-RBP1 
                 PAI-1 mRNA-binding protein 
                 AL080119 
               
               
                 SFPQ 
                 splicing factor proline/glutamine rich (polypyrimidine tract 
                 W27050 
               
               
                   
                 binding protein associated) 
               
               
                 AMACR 
                 alpha-methylacyl-CoA racemase 
                 AJ130733 
               
               
                 KIAA1045 
                 KIAA1045 protein 
                 AB028968 
               
               
                 HNRPH2 
                 heterogeneous nuclear ribonucleoprotein H2 (H′) 
                 U01923 
               
               
                 KIAA0537 
                 KIAA0537 gene product 
                 AB011109 
               
               
                   
                   
                 X55503 
               
               
                 MLLT2 
                 “myeloid/lymphoid or mixed-lineage leukemia (trithorax 
                 L13773 
               
               
                   
                 homolog,  Drosophila ); translocated to, 2” 
               
               
                 ELAVL3 
                 “ELAV (embryonic lethal, abnormal vision,  Drosophila )- 
                 D26158 
               
               
                   
                 like 3 (Hu antigen C)” 
               
               
                 ING1L 
                 “inhibitor of growth family, member 1-like” 
                 AI186701 
               
               
                 PPP4R1 
                 “protein phosphatase 4, regulatory subunit 1” 
                 U79267 
               
               
                 ACTB 
                 “actin, beta” 
                 X63432 
               
               
                 FBXO9 
                 F-box only protein 9 
                 AL031178 
               
               
                 LYPLA1 
                 lysophospholipase I 
                 AF081281 
               
               
                 POLR3F 
                 “polymerase (RNA) III (DNA directed) polypeptide F, 39 kDa” 
                 U93869 
               
               
                 MCLC 
                 Mid-1-related chloride channel 1 
                 AB018304 
               
               
                 PPIE 
                 peptidylprolyl isomerase E (cyclophilin E) 
                 AF042386 
               
               
                 PAICS 
                 “phosphoribosylaminoimidazole carboxylase, 
                 X53793 
               
               
                   
                 phosphoribosylaminoimidazole succinocarboxamide 
               
               
                   
                 synthetase” 
               
               
                 IFNGR2 
                 interferon gamma receptor 2 (interferon gamma 
                 U05875 
               
               
                   
                 transducer 1) 
               
               
                 PITPNM 
                 “phosphatidylinositol transfer protein, membrane- 
                 X98654 
               
               
                   
                 associated” 
               
               
                   
                   
                 X03453 
               
               
                 KIAA0435 
                 KIAA0435 gene product 
                 AB007895 
               
               
                 TAZ 
                 “tafazzin (cardiomyopathy, dilated 3A (X-linked); 
                 X92762 
               
               
                   
                 endocardial fibroelastosis 2; Barth syndrome)” 
               
               
                 ATP6V1H 
                 “ATPase, H+ transporting, lysosomal 50/57 kDa, V1 
                 AI741756 
               
               
                   
                 subunit H” 
               
               
                 DKFZP566C243 
                 DKFZP566C243 protein 
                 AL050274 
               
               
                 PPP1R3D 
                 “protein phosphatase 1, regulatory subunit 3D” 
                 Y18206 
               
               
                 SBA2 
                 CS box-containing WD protein 
                 AF038187 
               
               
                 MEF2A 
                 “MADS box transcription enhancer factor 2, polypeptide 
                 U49020 
               
               
                   
                 A (myocyte enhancer factor 2A)” 
               
               
                   
                   
                 J05614 
               
               
                 UNC13 
                 unc-13-like ( C. elegans ) 
                 AF020202 
               
               
                 HFL-EDDG1 
                 erythroid differentiation and denucleation factor 1 
                 AF048849 
               
               
                 LTA4H 
                 leukotriene A4 hydrolase 
                 J03459 
               
               
                 METTL1 
                 methyltransferase-like 1 
                 Y18643 
               
               
                   
                   
                 AD000092 
               
               
                   
                 “ Homo sapiens  cDNA FLJ40021 fis, clone 
                 AL080094 
               
               
                   
                 STOMA2006904” 
               
               
                 IFIT1 
                 interferon-induced protein with tetratricopeptide repeats 1 
                 M24594 
               
               
                 TEF 
                 thyrotrophic embryonic factor 
                 U44059 
               
               
                 HMOX2 
                 heme oxygenase (decycling) 2 
                 AI086057 
               
               
                 DDB1 
                 “damage-specific DNA binding protein 1, 127 kDa” 
                 U32986 
               
               
                 AKAP8 
                 A kinase (PRKA) anchor protein 8 
                 Y11997 
               
               
                 SLC9A1 
                 “solute carrier family 9 (sodium/hydrogen exchanger), 
                 S68616 
               
               
                   
                 isoform 1 (antiporter, Na+/H+, amiloride sensitive)” 
               
               
                 ACADM 
                 “acyl-Coenzyme A dehydrogenase, C-4 to C-12 straight 
                 M91432 
               
               
                   
                 chain” 
               
               
                 NEURL 
                 neuralized-like ( Drosophila ) 
                 AF029729 
               
               
                 CDKN1B 
                 “cyclin-dependent kinase inhibitor 1B (p27, Kip1)” 
                 AI304854 
               
               
                 ASH2L 
                 “ash2 (absent, small, or homeotic)-like ( Drosophila )” 
                 AB022785 
               
               
                 KHDRBS1 
                 “KH domain containing, RNA binding, signal transduction 
                 M88108 
               
               
                   
                 associated 1” 
               
               
                 SNAP25 
                 “synaptosomal-associated protein, 25 kDa” 
                 D21267 
               
               
                 RP2 
                 retinitis pigmentosa 2 (X-linked recessive) 
                 AJ007590 
               
               
                 ACAT2 
                 acetyl-Coenzyme A acetyltransferase 2 (acetoacetyl 
                 S70154 
               
               
                   
                 Coenzyme A thiolase) 
               
               
                 ATP6V1A1 
                 “ATPase, H+ transporting, lysosomal 70 kDa, V1 subunit 
                 L09235 
               
               
                   
                 A, isoform 1” 
               
               
                 AQP1 
                 “aquaporin 1 (channel-forming integral protein, 28 kDa)” 
                 U41518 
               
               
                 PPP1R8 
                 “protein phosphatase 1, regulatory (inhibitor) subunit 8” 
                 U14575 
               
               
                 HLA-DOB 
                 “major histocompatibility complex, class II, DO beta” 
                 X03066 
               
               
                 ENSA 
                 endosulfine alpha 
                 X99906 
               
               
                 MXI1 
                 MAX interacting protein 1 
                 L07648 
               
               
                 PSMD4 
                 “proteasome (prosome, macropain) 26S subunit, non- 
                 U51007 
               
               
                   
                 ATPase, 4” 
               
               
                 SLC6A2 
                 “solute carrier family 6 (neurotransmitter transporter, 
                 X91117 
               
               
                   
                 noradrenalin), member 2” 
               
               
                 GTF2I 
                 “general transcription factor II, i” 
                 U77948 
               
               
                   
                   
                 M35093 
               
               
                 ZFP36L2 
                 “zinc finger protein 36, C3H type-like 2” 
                 U07802 
               
               
                 NUP98 
                 nucleoporin 98 kDa 
                 AF042357 
               
               
                 MYOZ3 
                 myozenin 3 
                 AF052497 
               
               
                 NF1 
                 “neurofibromin 1 (neurofibromatosis, von 
                 D12625 
               
               
                   
                 Recklinghausen disease, Watson disease)” 
               
               
                   
                   Homo sapiens  mRNA; cDNA DKFZp564O0122 (from 
                 AL049951 
               
               
                   
                 clone DKFZp564O0122) 
               
               
                 PSMC2 
                 “proteasome (prosome, macropain) 26S subunit, 
                 D11094 
               
               
                   
                 ATPase, 2” 
               
               
                 PPP3CB 
                 “protein phosphatase 3 (formerly 2B), catalytic subunit, 
                 M29551 
               
               
                   
                 beta isoform (calcineurin A beta)” 
               
               
                 ITGA2B 
                 “integrin, alpha 2b (platelet glycoprotein IIb of IIb/IIIa 
                 M34480 
               
               
                   
                 complex, antigen CD41B)” 
               
               
                 FGF18 
                 fibroblast growth factor 18 
                 AF075292 
               
               
                 PYCR1 
                 pyrroline-5-carboxylate reductase 1 
                 M77836 
               
               
                 EIF4B 
                 eukaryotic translation initiation factor 4B 
                 X55733 
               
               
                 KIAA0806 
                 KIAA0806 gene product 
                 R93981 
               
               
                   
                 “ Homo sapiens  cDNA FLJ31348 fis, clone 
                 AI970189 
               
               
                   
                 MESAN2000026” 
               
               
                   
                   
                 AC002073 
               
               
                 MGC5576 
                 hypothetical protein MGC5576 
                 W27939 
               
               
                 UBE2E1 
                 “ubiquitin-conjugating enzyme E2E 1 (UBC4/5 homolog, 
                 AI039880 
               
               
                   
                 yeast)” 
               
               
                 JJAZ1 
                 joined to JAZF1 
                 D63881 
               
               
                 PMS1 
                 PMS1 postmeiotic segregation increased 1 ( S. cerevisiae ) 
                 U13695 
               
               
                 KIAA0240 
                 KIAA0240 protein 
                 D87077 
               
               
                 TBCD 
                 tubulin-specific chaperone d 
                 AJ006417 
               
               
                 NUP214 
                 nucleoporin 214 kDa 
                 X64228 
               
               
                 FOSL2 
                 FOS-like antigen 2 
                 X16706 
               
               
                 PAFAH1B1 
                 “platelet-activating factor acetylhydrolase, isoform Ib, 
                 L25107 
               
               
                   
                 alpha subunit 45 kDa” 
               
               
                 PSMA1 
                 “proteasome (prosome, macropain) subunit, alpha type, 
                 M64992 
               
               
                   
                 1” 
               
               
                   
                 ESTs 
                 AI184710 
               
               
                 APOBEC3B 
                 “apolipoprotein B mRNA editing enzyme, catalytic 
                 AL022318 
               
               
                   
                 polypeptide-like 3B” 
               
               
                   
                   
                 U18671 
               
               
                 H41 
                 hypothetical protein H41 
                 H15872 
               
               
                   
                   
                 HG4582-HT4987 
               
               
                 ORC1L 
                 “origin recognition complex, subunit 1-like (yeast)” 
                 U40152 
               
               
                 XDH 
                 xanthene dehydrogenase 
                 U39487 
               
               
                   
                   Homo sapiens  mRNA; cDNA DKFZp434M162 (from 
                 W72239 
               
               
                   
                 clone DKFZp434M162) 
               
               
                 FUBP3 
                 far upstream element (FUSE) binding protein 3 
                 U69127 
               
               
                 ID1 
                 “inhibitor of DNA binding 1, dominant negative helix-loop- 
                 S78825 
               
               
                   
                 helix protein” 
               
               
                 KIAA0637 
                 KIAA0637 gene product 
                 AB014537 
               
               
                 CLTB 
                 “clathrin, light polypeptide (Lcb)” 
                 M20470 
               
               
                 KIAA1094 
                 KIAA1094 protein 
                 AB029017 
               
               
                 RAB1A 
                 “RAB1A, member RAS oncogene family” 
                 M28209 
               
               
                 ERCC6 
                 “excision repair cross-complementing rodent repair 
                 L04791 
               
               
                   
                 deficiency, complementation group 6” 
               
               
                 MYT1 
                 myelin transcription factor 1 
                 AB028973 
               
               
                 MGC10471 
                 hypothetical protein MGC10471 
                 X13956 
               
               
                 C12orf8 
                 chromosome 12 open reading frame 8 
                 X94910 
               
               
                 MSL3L1 
                 male-specific lethal 3-like 1 ( Drosophila ) 
                 AL050178 
               
               
                 CSTF2T 
                 likely ortholog of mouse variant polyadenylation protein 
                 AB014589 
               
               
                   
                 CSTF-64 
               
               
                 GS3955 
                 GS3955 protein 
                 D87119 
               
               
                   
                   
                 U14573 
               
               
                 MTA1 
                 metastasis associated 1 
                 U35113 
               
               
                 FLJ20619 
                 hypothetical protein FLJ20619 
                 AL049431 
               
               
                 DNAJC7 
                 “DnaJ (Hsp40) homolog, subfamily C, member 7” 
                 W28595 
               
               
                 TFRC 
                 “transferrin receptor (p90, CD71)” 
                 X01060 
               
               
                 KIAA0218 
                 KIAA0218 gene product 
                 D86972 
               
               
                 KIAA1089 
                 KIAA1089 protein 
                 AB029012 
               
               
                 FCGR2A 
                 “Fc fragment of IgG, low affinity IIa, receptor for (CD32)” 
                 M31932 
               
               
                 CSNK1A1 
                 “casein kinase 1, alpha 1” 
                 L37042 
               
               
                 HPS1 
                 Hermansky-Pudlak syndrome 1 
                 U65676 
               
               
                 ACK1 
                 activated p21cdc42Hs kinase 
                 L13738 
               
               
                 MAP-1 
                 modulator of apoptosis 1 
                 AI670788 
               
               
                 DDX9 
                 “DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 9 (RNA 
                 L13848 
               
               
                   
                 helicase A, nuclear DNA helicase II; leukophysin)” 
               
               
                 FAM8A1 
                 “family with sequence similarity 8, member A1” 
                 AL050128 
               
               
                 PRO2730 
                 hypothetical protein PRO2730 
                 AL045811 
               
               
                   
                   Homo sapiens  mRNA; cDNA DKFZp586H201 (from 
                 AL049430 
               
               
                   
                 clone DKFZp586H201) 
               
               
                 KIAA0146 
                 KIAA0146 protein 
                 D63480 
               
               
                 NUDEL 
                 LIS1-interacting protein NUDEL; endooligopeptidase A 
                 AF038203 
               
               
                 ARC 
                 activity-regulated cytoskeleton-associated protein 
                 D87468 
               
               
                 HMBS 
                 hydroxymethylbilane synthase 
                 M95623 
               
               
                 TRA1 
                 tumor rejection antigen (gp96) 1 
                 X15187 
               
               
                   
                   
                 U12471 
               
               
                 DAP 
                 death-associated protein 
                 X76105 
               
               
                 RYBP 
                 RING1 and YY1 binding protein 
                 AL049940 
               
               
                 RGS19 
                 regulator of G-protein signalling 19 
                 X91809 
               
               
                 BMP10 
                 bone morphogenetic protein 10 
                 AF101441 
               
               
                 KIAA0492 
                 KIAA0492 protein 
                 AB007961 
               
               
                 URKL1 
                 uridine kinase-like 1 
                 AI249721 
               
               
                 SFRS2 
                 “splicing factor, arginine/serine-rich 2” 
                 X75755 
               
               
                 CAPNS1 
                 “calpain, small subunit 1” 
                 X04106 
               
               
                 C1orf8 
                 chromosome 1 open reading frame 8 
                 Z78368 
               
               
                 UBE3B 
                 ubiquitin protein ligase 
                 AI749193 
               
               
                 E2F3 
                 E2F transcription factor 3 
                 D38550 
               
               
                   
                   
                 J04423 
               
               
                 USP1 
                 ubiquitin specific protease 1 
                 AB014458 
               
               
                 TNRC15 
                 trinucleotide repeat containing 15 
                 AB014542 
               
               
                 IL5RA 
                 “interleukin 5 receptor, alpha” 
                 M75914 
               
               
                   
                   
                 X03453 
               
               
                 RHEB2 
                 Ras homolog enriched in brain 2 
                 D78132 
               
               
                 LSM6 
                 Sm protein F 
                 AA917945 
               
               
                 TBX5 
                 T-box 5 
                 Y09445 
               
               
                   
                   Homo sapiens  mRNA; cDNA DKFZp451N147 (from 
                 AA534868 
               
               
                   
                 clone DKFZp451N147) 
               
               
                 ARSE 
                 arylsulfatase E (chondrodysplasia punctata 1) 
                 X83573 
               
               
                 LCP1 
                 lymphocyte cytosolic protein 1 (L-plastin) 
                 J02923 
               
               
                 CSF1 
                 colony stimulating factor 1 (macrophage) 
                 M37435 
               
               
                 DHCR7 
                 7-dehydrocholesterol reductase 
                 AF034544 
               
               
                   
               
             
          
         
       
     
         [0048]    Recent technical developments have now facilitated the analysis of large numbers of genes by means of the use of high density microarrays or “chips”. Each location on such a chip contains a sequence related to a specific sequence, such that when a signal (such as a visual color, produced by the use of suitable colored conjugate) is present, it can be readily related to the binding of sequences specific for a particular gene, the identity of which is determined by the position of the signal in the array. Suitable computer programs may then be used to analyze and present (in graphical and/or tabular form) the data extracted from the microarray signals. In addition to providing information relating to the expression of specific genes, high density microarrays may also be used to generate “fingerprints” which are characteristic of, for example, a particular disease, treatment response or (as in the case of the invention disclosed herein) prognostic group. The fingerprint thus obtained may be subjected to analysis by any of a number of statistical techniques (including cluster analysis, as described in the illustrative example, hereinbelow), in order to assign said fingerprint to a discrete results group. The results group may be one of a binary pair (such as the good prognosis/poor prognosis pair of the present invention), or it may be one of a more complex series of groups (such as in the case of the differential diagnosis of several pathological possibilities.) 
         [0049]    Suitable high density microarrays may either be purchased “off-the-shelf”, pre-loaded with an array of oligonucleotide sequences (for example the Genechip Human Genome arrays produced by Affymetrix, Santa Clara, Calif., USA), or alternatively may be custom-produced such that they bear a subset of the total genome, wherein said subset is relevant for the desired diagnostic, prognostic or drug discovery application of the microarray. Many different materials and techniques may be used in the construction of high density microarrays, the details of which appear in many publications including U.S. Pat. No. 6,344,316, which is in its entirety incorporated herein by reference. 
         [0050]    The techniques used to obtain, purify and hybridize RNA and other nucleic acids are varied and well known to all skilled artisans in the field. Details of many such suitable techniques are to be found in standard reference works such as the book “Molecular cloning: a laboratory manual” by Sambrook, J., Fritsch, E. F. &amp; Maniatis, T., Cold Spring Harbor, N.Y., 2 nd  ed., 1989 (and all later editions), which is incorporated herein by reference in its entirety. 
         [0051]    In addition, Methods of isolating total mRNA are described in detail in Chapter 3 of Laboratory Techniques in Biochemistry and Molecular Biology: Hybridization with Nucleic Acid Probes, Part I. Theory and Nucleic Acid Preparation, P. Tijssen, ed. Elsevier, N.Y. (1993). More specific information related to the use of polymerase chain reaction (PCR) techniques may be gleaned from “Innis et al. eds.,  PCR Protocols: A guide to method and applications ”, which is incorporated herein by reference. 
         [0052]    Following isolation of the nucleic acids sequences and their purification and hybridization to a suitable high density chip, binding is determined by means of a suitable detection method. In a preferred embodiment, the hybridized nucleic acids are 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. Labels may be introduced either during the course of the synthesis of the nucleic acid sequences (e.g. during a PCR reaction) or as a discrete post-synthetic step. Detectable labels suitable for use in the present invention include any composition detectable by spectroscopic, photochemical, biochemical, immunochemical, electrical, optical or chemical means. Particularly preferred are labels such as biotin for staining with labeled streptavidin conjugate, magnetic beads (e.g., Dynabeads™), fluorescent dyes (e.g., fluorescein, texas red, rhodamine, green fluorescent protein, and the like (obtainable from Molecular Probes, Eugene, Oreg., USA). However, other label types, including radiolabels and enzymes may also be usefully employed. 
         [0053]    Several different types of microarray may be used or produced in order to work the present invention. Thus, a variety of different substrate types, including (but not limited to) metal oxides, nylon, ceramic material and glasses may be used to construct the microarray. In a commonly-used configuration, the microarray is constructed such it has a surface area less than 6.25 cm 2 , preferably in the range of about 1.6 cm 2  to 6.25 cm 2 . Details of the construction of microarrays suitable for use in the present invention are now well known in the art, and may be obtained from a variety of publications including the aforementioned U.S. Pat. No. 6,344,316, U.S. Pat. No. 6,232,068 and U.S. Pat. No. 5,510,270, all of which are incorporated herein in their entirety. 
         [0054]    The following example is provided for illustrative purposes and in order to more particularly explain and describe the present invention. The present invention, however, is not limited to the particular embodiments disclosed in the example. 
       Example 1 
     Prognosis Determination by Means of Genetic Profiling of Tumor Material Obtained from ES Patients 
     Methods 
     Patient Samples 
       [0055]    Fourteen primary tumor specimens and six metastases were obtained from 18 ES patients with non-metastatic disease. In the case of one patient, both primary and recurrent tumors were analyzed (SA37 and SA43), and two metastases were taken from another patient, six years apart (SA45 and SA46). All patients were admitted to the Pediatric Hematology Oncology Department at Schneider Children&#39;s Medical Center, Petach Tikva, Israel. Informed consent was obtained from the patients or their guardians, and the local and National Ethics Committees approved the research project. All patients were treated with a combination of aggressive chemotherapy, radiotherapy and surgery. Median age at diagnosis was 15 years (range 7-27). Five patients were females and 13 were males. Response to therapy was defined by histopathological response and assessed by percentage of tumor necrosis at the time of surgery (limb salvage procedure) following neoadjuvant chemotherapy and radiotherapy. Median follow up was 72.5 months (range 7-171). Tumors were snap-frozen in liquid nitrogen immediately after surgery and stored at −80° C. until use. 
       Microarray Hybridization 
       [0056]    Ten μg of total RNA was extracted from each tumor using Tri Reagent (Molecular Research Center, Inc. Cincinnati, Ohio). Double stranded cDNA was generated from 10 ug of total RNA using the SuperScript Choice System from Gibco Brl (Rockville, Md., USA), using an oligo(dT) 24  primer containing a T7 promoter site at the 3′ end (Genset, La Jolla, Calif.). cDNAs were purified via a phenol-chloroform extraction followed by an ethanol precipitation. Purified cDNA was used as template for In vitro transcription (IVT), which was performed with T7 RNA polymerase and biotin-labeled ribonucleotides, using the ENZO BioArray High Yield RNA Transcript Labeling Kit (Enzo Diagnostics, New York, N.Y.). Labeled in vitro transcripts were purified over RNeasy mini columns (Qiagen, Valencia, Calif.) according to manufacturer&#39;s instructions. The labeled cRNA was fragmented at 94° C. for 35 min in fragmentation buffer (40 mM Tris-acetate, pH 8.1/100 mM potassium acetate, 30 mM magnesium acetate), and a hybridization mix was generated by addition of herring sperm DNA (0.1 mg/ml), acetylated BSA (0.5 mg/ml, Invitrogen), sodium chloride (1 M), Tris-acetate (10 mM), and Tween-20 (0.0001%). A mixture of four control bacterial and phage cRNA (1.5 pM BioB, 5 pM BioC, 25 pM BioD, and 100 pM Cre) was included to serve as an internal control for hybridization efficiency. 
         [0057]    Aliquots of each sample (12 μg cRNA in 200 μl hybridization mix) were hybridized to a Genechip Human Genome U95Av2 array (Affymetrix, Santa Clara, Calif., USA). After hybridization, each array was washed according to procedures developed by the manufacturer (Affymetrix), and stained with streptavidin-phycoerythrin conjugate (Molecular Probes, Eugene, Oreg.). The hybridization signal was amplified by using biotinylated anti-streptavidin antibodies (Vector Laboratories, Burlingame, Calif.), followed by restaining with streptavidin phycoerythrin. Arrays were scanned by the GeneArray scanner G2500A (Hewlett Packard, Palo Alto, Calif.), and scanned images were visually inspected for hybridization imperfections. Arrays were analyzed using Genechip 4.1 software (Affymetrix). The expression value for each gene was determined by calculating the average differences of the probe pairs in use for that gene. 
         [0058]    Two samples were analyzed in duplicate and results were reproducible. 
       Data Analysis: 
     Normalization and Filtering 
       [0059]    The microarray results were analyzed using the GeneSpring Software®. Normalization was performed by setting expression values lower than zero to zero and than each measurement was divided by the median of all measurements in that sample. 
         [0060]    In order to filter out genes that are not expressed in any of the groups, Affymetrix absolute call (MAS 4.0: P, M—expressed genes, A—not expressed) was used. Genes that were expressed in one group were defined as genes expressed in at least 3 samples. 
       Selecting for Differentially Expressed Genes 
       [0061]    A Student&#39;s t-test was applied for each gene, and genes with an adjusted P-value less then 0.01 were selected as differentially expressed genes. P-values were corrected to reduce false positive using Benjamini and Hochberg False Discovery Rate (Benjamini, Y. et al. J. Roy. Stat. Soc. B., 57, 289-300 (1995)]. 
       Hierarchical Clustering 
       [0062]    Divisive hierarchical clustering [Everitt, B. S. Cluster analysis. 3 rd  edition, 62-65 (Arnold, London, 1993)) was performed as described by Eiesen et al. [Eisen, M. B. et al.  Proc. Natl. Acad. Sci. USA  95, 14863-14868 (1998], using centered correlation as the measurement distance. 
       Progression Free Survival Analysis 
       [0063]    Kaplan-Meier progression free survival analysis, using the log rank test, was performed in order to correlate the microarray classification results with patients&#39; clinical outcome. 
       Quantitative Real Time PCR (RQ-PCR) 
       [0064]    The microarray derived expression data was evaluated for the cadherin-11 and MTA1 genes using quantitative PCR by the LightCycler system (Roche Diagnostics, Manheim, Germany). cDNA was prepared using the Reverse Transcription System (Promega Corporation, Madison, Wis.) and purified with GFX PCR DNA and Gel. Band Purification kit (Amersham Biosciences, Piscataway, N.J.). 5 μl was amplified in a 20 μl reaction containing 4 mM MgCL 2 , 5 μM of each primer and LightCycler—FastStart DNA Master SYBR Green I mix (Roche Diagnostics). 
         [0000]    Cadherin-11 primers: sense 5′-AGAGGCCTACATTCTGAACG-3′ and
 
antisense 5′-TTCTTTCTTTTGCCTTCTCAGG-3′. MTA1 primers:
 
sense 5′-AGCTACGAGCAGCACAACGGGGT-3′ and
 
antisense 5′-CACGCTTGGTTTCCGAGGAT-3′.
 
         [0065]    All examinations were performed in duplicate and data analysis was done using the LightCycler Software. 
       Results 
       [0066]    The study included 14 tumor samples from localized ES patients. The gene expression profile of 7 tumors from patients who had progressed between 5 months up to 5 years from diagnosis (defined as High Risk—HR) was compared with 7 tumors from patients who were disease free for a long period of follow up (median 92 months; range 66-171) (defined as Low Risk—LR). 
         [0067]    In brief, RNA was isolated from each tumor and hybridized to Affymetrix oligonucleotide high-density arrays U95Av2. A subset of genes that distinguish between the two groups (HR and LR) by two steps was identified. Firstly, 8098 genes that were expressed in one of the groups, in at least 3 samples, were selected. Subsequently, 818 genes differentially expressed in either the HR or the LR groups (t-test; P&lt;0.01) were studied. These 818 most significant genes are listed in Table 1, hereinabove. 
         [0068]    In order to control false positive results as a consequence of multiple comparisons, the P values were adjusted using the False Discovery Rate (FDR) method [Everitt, B. S. Cluster analysis. 3 rd  edition, 62-65 (Arnold, London, Benjamin, Y. et al., J. Roy. Stat. Soc. B, 57, 289-300 (1995)]. 
         [0069]    Using hierarchical clustering, based on the 818 genes, for prognosis profile, two distinct clusters could be determined: poor and good prognosis signatures ( FIG. 1   a ). All of the seven HR and six out of the seven LR patients (86%) were classified as poor and good prognosis signatures, respectively (Table 2). One clinically LR patient who was disease free for a long period of follow up (97 months), was classified in the poor prognosis signature group. Each one of the 818 genes is sufficient for the prediction of prognosis. 
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 2 
               
             
             
               
                   
               
               
                 Clinical data, disease course and results of 
               
               
                 molecular classification 
               
             
          
           
               
                   
                   
                   
                   
                   
                   
                 Microarray 
               
               
                   
                   
                   
                 Response 
                   
                   
                 classification 
               
               
                   
                 Age 
                 Primary 
                 to therapy 
                 Relapse 
                 Outcome 
                 prognosis 
               
               
                 Sample 
                 (years) 
                 Site 
                 % necrosis 
                 (months) 
                 (months) 
                 group 
               
               
                   
               
             
          
           
               
                 High Risk 
                   
                   
                   
                   
                   
                   
               
               
                 SA3 
                 21 
                 Pelvis 
                 &lt;90% 
                 Local (5) 
                 EX (7) 
                 Poor 
               
               
                 SA37 
                 7 
                 Cranium 
                 N.D 
                 Local (29) 
                 EX (44) 
                 Poor 
               
               
                 SA38 
                 17 
                 Pelvis 
                 &lt;90% 
                 Local (10) 
                 EX (18) 
                 Poor 
               
               
                 SA47 
                 20 
                 Pelvis 
                 &gt;90% 
                 Cranium (61) 
                 AWD (76) 
                 Poor 
               
               
                 SA75 
                 18 
                 Pelvis 
                 &lt;90% 
                 Local (27) 
                 EX (49) 
                 Poor 
               
               
                 SA78 
                 24 
                 Femur 
                 &lt;90% 
                 Lung (47) 
                 EX (65) 
                 Poor 
               
               
                 SA79 
                 12 
                 Pelvis 
                 &gt;90% 
                 Bone (41) 
                 EX (60) 
                 Poor 
               
               
                 Low Risk 
               
               
                 SA2 
                 15 
                 Pelvis 
                 &gt;90% 
                 — 
                 NED (103) 
                 Poor 
               
               
                 SA4 
                 14 
                 Chest 
                 N.D 
                 — 
                 NED (92) 
                 Good 
               
               
                 SA5 
                 13 
                 Radius 
                 &lt;90% 
                 — 
                 NED (66) 
                 Good 
               
               
                 SA9 
                 13 
                 Tibia 
                 &gt;90% 
                   
                 NED (168) 
                 Good 
               
               
                 SA80 
                 15 
                 Pelvis 
                 &gt;90% 
                 — 
                 NED (81) 
                 Good 
               
               
                 SA81 
                 14 
                 Pelvis 
                 &gt;90% 
                 — 
                 NED (82) 
                 Good 
               
               
                 SA82 
                 11 
                 Tibia 
                 &gt;90% 
                   
                 NED (173) 
                 Good 
               
               
                 Metastases 
               
               
                 SA43 
                 7 
                 Cranium 
                 N.D 
                 Local (29) 
                 EX (44) 
                 Poor 
               
               
                 SA44 
                 27 
                 Femur 
                 &gt;90% 
                 Lung (61) 
                 NED (91) 
                 Good 
               
               
                 SA45 
                 16 
                 Femur 
                 &lt;90% 
                 Brain (128) 
                 AWD (151) 
                 Poor 
               
               
                 SA46 
                 16 
                 Femur 
                 &lt;90% 
                 Lung (67) 
                 AWD (151) 
                 Poor 
               
               
                 SA76 
                 20 
                 Pelvis 
                 &lt;90% 
                 Lung (24) 
                 EX (44) 
                 Poor 
               
               
                 SA77 
                 8 
                 Pelvis 
                 &lt;90% 
                 Local (37) 
                 EX (104) 
                 Good 
               
               
                   
               
               
                 EX = Expired; 
               
               
                 NED = No Evidence of Disease; 
               
               
                 AWD = Alive With Disease 
               
               
                 Numbers in brackets = time from diagnosis; 
               
               
                 N.D = not done 
               
             
          
         
       
     
         [0070]    Kaplan-Meier life table analysis indicated that the patients predicted to have a good prognosis signature had a significantly improved progression free survival (PFS) compared with those predicted to have a poor prognosis signature ( FIG. 1   b , P=0.002). 
         [0071]    Additionally, the genes were reordered into 2 major clusters that were divided into 6 sub-clusters, by performing hierarchical clustering of all signature genes ( FIG. 1   c ). The two major groups correspond to (i) over-expressed in the poor prognosis group and down-regulated in the good prognosis group, and (ii) vice versa. The six sub-clusters correspond to the variability of genes among the patients with poor or good prognosis signatures, which was more considerable in the poor prognosis group. Genes that were over-expressed in the poor prognosis patients include known markers of ES like EWS breakpoint region 1 and beta 2 microglobulin, genes regulating the cell cycle like CDK2, E2F, RAF and MAPKs, and genes associated with invasion and metastasis like cadherin-11 and MTA1. The last two belong to subclusters 5 and 6, genes which were homogeneously expressed in all patients. Down-regulated genes in the poor prognosis patients, included tumor suppressor genes like FHIT and LLGL1, genes inducing apoptosis like TNFRSF12, TGFB1, CASP10 and TP63 and inhibitors of angiogenesis like IFIT1 and IRF2. 
         [0072]    Two genes that were significantly over expressed in the poor prognosis signature group (p&lt;0.01) are of particular interest; both are associated with invasion and metastasis. The first one is cadherin11 (OB-cadherin), a homophilic calcium-dependent cell adhesion molecule, and the second is MTA1, tumor metastasis-associated gene. Cadherins modulate calcium ion-dependent cell-cell adhesion and are important in cell aggregation, migration and sorting. Defective cell-cell and cell-matrix adhesion are among the hallmarks of cancer. Disruption of the cadherin-catenin complex has been demonstrated in carcinomas arising in several tissues including prostate, gastric and breast carcinomas, and has been correlated with various pathologic and clinical features, such as tumor differentiation, proliferation and a poor patient prognosis. 
         [0073]    The MTA1 gene is a novel, highly conserved gene that encodes a nuclear protein product. Examination of the MTA1 protein suggests that it is a histone deacetylase and may serve multiple functions in cellular signaling, chromosome remodeling and transcription processes that are important in the progression, invasion and growth of metastatic cells. The gene has been found to be over-expressed in a variety of human cell lines (breast, ovarian, lung, gastric and colorectal) and cancerous tissues (breast, esophageal, colorectal, gastric and pancreatic cancer). 
         [0074]    To validate the microarray data, these two over-expressed genes were analyzed in further detail using reverse transcriptase—quantitative Real Time PCR (RQ-PCR). Microarray-based expression and RQ-PCR based expression data correlated significantly ( FIGS. 2   a  and  b ). The mean log expression value of the poor prognosis signature group is significantly higher than that of the good prognosis signature group for both genes, cadherin-11 and MTA1, P=0.024 and P=0.003, respectively. 
         [0075]    Six metastases from localized patients who progressed were further tested, using the unsupervised learning methodology, whether the poor and good prognosis signature set of genes can classify metastatic tissues to one of the prognostic groups, or as a distinct group. 
         [0076]    While specific embodiments of the invention have been described for the purpose of illustration, it will be understood that the invention may be carried out in practice by skilled persons with many modifications, variations and adaptations, without departing from its spirit or exceeding the scope of the claims.

Technology Classification (CPC): 2