Abstract:
The present invention relates to the identification a molecular signature for PTEN tumor suppressor. The molecular signature comprising a gene or genes that are of use for diagnosis, prognosis, drug research and development and therapeutics. Specifically, the present invention relates to identification of IGFBP2 gene, its mRNA and/or protein products that closely associate with PTEN mutations. The present invention further demonstrates that IGFBP2 expression is negatively regulated by PTEN, positively regulated by PI3K and Akt activation, that IGFBP2 plays a functional role in the PTEN signaling and is required for Akt transformation. The use of IGFBP2 gene, its gene product such as its RNA transcript, protein and molecular probes in diagnosis, prognosis, drug discovery and validation and therapeutic target and therapeutics is also contemplated.

Description:
BACKGROUND OF THE PRESENT INVENTION  
       [0001]     1. Field of Invention  
         [0002]     The present invention relates to the identification of genes and their products including their coding protein products that are useful in diagnostics, prognostics and therapeutics of human tumors. In particular, the present invention relates to a set or sets of genes and their products that are associated with tumor suppressor gene PTEN abnormalities, such as PTEN gene deletions, loss of heterozygosity and/or mutations. The present invention relates further to genes and their products that are associated with PTEN-regulated cellular processes, in particular, the PI3K- and/or Akt signal transduction pathways and activations.  
         [0003]     2. Description of Related Arts  
         [0004]     The PTEN/MMAC1/TEP1 tumor suppressor gene was identified by genomic representational difference analysis (RDA) on human cancer tissues (1), by positional cloning to the genomic locus mutated in multiple advanced cancers (2), and by homologous search for novel protein tyrosine phosphatase (3). This gene is located on human chromosome 10q23, a genomic locus with frequent loss of heterozygosity in multiple advanced cancers. It encodes a protein of 403 amino acids with sequence highly homologous to protein tyrosine phosphatase and the cytoskeletal proteins tensin and auxilin. Germline mutations of PTEN are associated with Cowden and Bannayan-Zonana syndromes, two autosomal dominant disorders characterized as harmartomas with increased susceptibility to cancer (4-6). Somatic mutations of this gene are found in many human cancers, including glioblastoma and prostate cancer with a frequency of up to 50%. Homozygous deletion of the PTEN gene is lethal and heterozygous deletion results in tumor formation in several organs in mice (7-9). These data indicate that PTEN is an important tumor suppressor for a variety of cancers.  
         [0005]     One of the well-characterized functions for PTEN is lipid phosphatase activity. This activity dephosphorylates phosphatidylinositol triphosphate at the D3 position, reducing the amount of an important signal transduction molecule produced by PI3K in response to many growth factors, such as insulin-like growth factor 1(IGF-1) that is implicated in tumor formation (10, 11). This PI3K-antagonizing activity in turn inhibits activation of its downstream effector Akt and leads to inhibition of cell survival and proliferation, cellular processes essential for tumor formation and progression (12). In addition to its lipid phosphatase activity, PTEN is also a tyrosine phosphatase that reduces the tyrosine phosphorylation of the focal adhesion kinase (FAK), indicating that PTEN also negatively regulates interactions with the extracellular matrix (13). Furthermore, PTEN deleted mouse fibroblasts have an enhanced cell motility compared to its isogenic wild-type lines. This enhanced cell motility is associated with increased activities of Rac and Cdc42 through its lipid phosphatase activity (14). Taken together, these data indicate that PTEN regulates many cellular processes through a complex map of signal transduction pathways.  
         [0006]     Global gene expression analysis is a useful tool to classify and identify tumor types (15, 16), to identify gene involved in tumor formation and progression (17, 18), and predict clinical outcome of cancer patients (19). Recently, it has also been used to identify signatures for tumor metastasis (20). However, its application to identify molecular signatures of a signal transduction pathway involved in tumor formation and progression has not been reported.  
       SUMMARY OF THE PRESENT INVENTION  
       [0007]     The present invention relates to the identification of genes and their products including their coding protein products that are useful in diagnostics, prognostics and therapeutics of human tumors. In particular, the present invention relates to a set or sets of genes and their products that are associated with tumor suppressor gene PTEN abnormalities, such as PTEN gene deletions, loss of heterozygosity and/or mutations. The present invention relates further to genes and their products that are associated with PTEN-regulated cellular processes, in particular, the PI3K- and/or Akt signal transduction pathways and activations.  
         [0008]     The present invention utilizes global gene expression profiling analyses employing gene chip technology to identify transcriptional targets downstream of the complex signal transduction pathways of PTEN. Gene expression profiling was performed on prostate cancer and giloblastoma, two cancer types frequently affected by PTEN mutations. These global gene expression analyses identify a molecular signature that can accurately classify tumor samples according to its PTEN status regardless of tumor types. Extensive studies were carried out for IGFBP2 gene and its protein products, the most significant gene in the signature. It was demonstrated that IGFBP2 is biochemically regulated by PTEN and plays a functional role in PTEN function.  
         [0009]     In one embodiment of present invention, a set of genes consists of 490 genes as listed in Table 2 with the Gini index number from highest to the lowest were identified and evaluated for their predictive power of associating with the PTEN status in tumors.  
         [0010]     In another embodiment of present invention, a set of genes comprising 12 genes with the highest Gini index were identified and evaluated individually and combined for their predictive power of associating with the PTEN status in tumors.  
         [0011]     These genes include insulin-like growth factor binding protein 2 or IGFBP2 (Accession numbers X16302 and S37730), a hypothetical protein (Acc# AF052186), TUA8 Cri-du-chat region (Acc# AF009314), dual specificity phosphatase 10 or MPK-5 (Acc# AB026436), Neuralized (Acc# AF029729), regulator of G-protein signaling 1 or RGS-1 (Acc# S59049), expressed in activated T/LAK lymphocytes or LAP-4p (Acc# AB002405), gamma-tubulin complex protein 2 or GCP2 (Acc# AF042379), human AMP deaminase gene or AMPD3 (Acc# U29926), PFTAIRE protein kinase 1 or PFTK1 (Acc# AB020641), and pleckstrin homology, sec 7 and coiled/coid domains 1 or cytohesin 1 (Acc# M85169).  
         [0012]     In yet another embodiment of present invention, individual gene of the above said 12 genes is identified as useful in associating with the PTEN status in tumors, thus, the establishment of diagnostic, prognostic and therapeutic values of these genes and/or their RNA transcripts and/or protein products in human tumors associated with PTEN abnormalities.  
         [0013]     In yet another embodiment of present invention, the IGFBP2 gene and its RNA and protein products are identified as closely associated with the PTEN gene abnormalities such as deletions, mutations and loss of heterozygosity.  
         [0014]     In a further embodiment of present invention, the IGFBP2 gene and its RNA and protein products are identified to be associated with P13K signal transduction pathway, in particular, PI3K activation and inhibition.  
         [0015]     In a further embodiment of present invention, the IGFBP2 gene and its RNA and protein products are identified to be associated with Akt signal transduction pathway, in particular, Akt phosphorylation through activation or inhibition.  
         [0016]     In one embodiment of present invention, a diagnostic and/or prognostic product comprising an antibody against the IGFBP2 provides diagnostic and/or prognostic value in associating tumor staging and grading in association with PTEN status.  
         [0017]     In a further embodiment of present invention, the IGFBP2 gene and its RNA and protein products are useful in the screening and selection of therapeutic useful drugs against human cancers.  
         [0018]     In another embodiment of present invention, a diagnostic and/or prognostic product comprising an antibody against the IGFBP2 is useful in screening and selecting a therapeutic drug for treating human cancers.  
         [0019]     In further embodiment of present invention, the IGFBP2 gene, its product such as RNA transcript and/or protein product are useful in designing, screening, validating and developing a therapeutically useful drug or means such as a dominant negative IGFBP2 that is useful in abolishing IGFBP2 normal and/or abnormal functions in promoting cancer formation, progression, antisense RNA, antisense oligonucleotide and/or siRNAi compounds, or shRNA gene knockdown technology that suppress or erase IGFBP2 gene expression or reduce its RNA transcript level; antibodies that neutralize IGFBP2 functionalities, gene therapies that embody the IGFBP2 gene.  
         [0020]     In another embodiment of present invention, a diagnostic and/or prognostic product comprising an antibody against the IGFBP2 provides diagnostic and/or prognostic value in predicting the effectiveness and/or responsiveness of a therapeutics for treating human cancers.  
         [0021]     In one embodiment of present invention, a diagnostic and/or prognostic product comprising a molecular probe in the forms of a nucleic acid molecule such as oligonucleotide, DNA and/or RNA molecule with its nucleotide sequence homologous or complementary to the gene sequence of the IGFBP2 gene provides diagnostic and/or prognostic value in associating tumor staging and grading in association with PTEN status.  
         [0022]     In one embodiment of present invention, a diagnostic and/or prognostic product comprising a molecular probe in the forms of a nucleic acid molecule such as oligonucleotide, DNA and/or RNA molecule with its nucleotide sequence homologous or complementary to the gene sequence of the IGFBP2 gene is useful in the screening and selection of therapeutic useful drugs against human cancers.  
         [0023]     In one embodiment of present invention, a diagnostic and/or prognostic product comprising a molecular probe in the forms of a nucleic acid molecule such as oligonucleotide, DNA and/or RNA molecule with its nucleotide sequence homologous or complementary to the gene sequence of the IGFBP2 gene provides diagnostic and/or prognostic value in predicting the effectiveness and responsiveness of a therapeutics for human cancers.  
         [0024]     In another embodiment of present invention, a diagnostic and/prognostic product comprising a gene probe or an antibody against its product is useful in diagnosis and/or prognosis of human cancers, in selecting and screening a therapeutic compounds of means for treating human cancers and/or in predicting effectiveness and responsiveness of a therapeutic means including a therapeutic drug in the treatment of human cancers. The above said gene is selected from a group of 490 genes enlisted in the Table 2, in particular, is selected from a group of genes consisting the followings 12 genes: insulin-like growth factor binding protein 2 or IGFBP2 (accession numbers X16302 and S37730), a hypothetical protein (ACC# AF052186), TUA8 CRI-DU-CHAT region (ACC#AF009314), dual specificity phosphatase 10 or MPK-5 (ACC# AB026436), neuralized (ACC# AF029729), Regulator of G-Protein Signaling 1 or RGS-1 (ACC#S59049), expressed in activated T/LAK lymphocytes or LAP-4P (ACC# AB002405), gamma-tubulin complex protein 2 or GCP2 (ACC# AF042379), human amp dearninase gene or AMPD3 (ACC# U29926), pftaire protein kinase 1 or PFTK1 (ACC# AB020641), and pleckstrin homology, SEC 7 and coiled/coid domains 1 or cythohesin 1 (ACC# M85169).  
         [0025]     The present invention relates with utilizing the above identified genes in Table 2, in particular the above said 12 genes, especially the IGFBP2 gene and its products as drug target in screening and selecting therapeutically useful compounds and/or means for the treatment of human cancers. 
     
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0026]      FIG. 1 . Molecular signature of the PTEN tumor suppressor. A. Predictive power of each gene represented by Gini index. B. Ability of sets of genes to predict PTEN status. C. 12 genes separate tumors according to the PTEN status. D. Hierachical clustering of genes against tumors.  
         [0027]      FIG. 2 . Upregulation of IGFBP-2 in PTEN mutated tumors. (A, B, C) Western blot analysis of prostate cancer xenograft samples (A), glioblastoma tissue samples (B and C). D and E. Radioassay for hIGFBP2 in culture media (D) and serum of mice carrying xenograft tumors (E).  
         [0028]      FIG. 3 . IGFBP2 is regulated by the PTEN/Akt pathway. Western blot analysis of the PTEN-mutated or wild type mouse embryonic fibroblasts (A), LNCaP cells treated with vehicle or PI3K inhibitor (13), LAPC4 cells with or without overexpression of constitutive-active Akt (C).  
         [0029]      FIG. 4 . IGFBP2 rescued growth inhibition by PTEN. Acutely infected PC3 cells with viruses carrying different cDNAs were subject to cell count (A) or cell cycle analysis (B), and the IGFBP2 expression was determined by western blot analysis (C).  
         [0030]      FIG. 5 . IGFBP2 plays a functional role in the PI3K-Akt pathway. (A) Cell cycle analysis of vector or IGFBP2 infected LNCaP cells treated with PI3K inhibitor (LY294002). (B and C) Clonagenic assay on wild-type or IGFBP2 knockout mouse embryonic fibroblasts with or without constitutive-active Akt expression (B), or myc expression (C).  
         [0031]      FIG. 6 . IGFBP2 knockdown decreased the growth of PTEN mutated prostate cancer cells, an effect identical to re-introduction of exogenous wild-type PTEN. Top panel, cell count on vector, shRNA targeting IGFBP2, or PTEN infected PC3 cells; bottom panel, western blot analysis on the engineered cells. p  FIG. 7 . (A) Overexpression of AR is the cause of hormone refractory prostate cancer. (B) Hormone refractory prostate cancer is still ligand dependent refractory prostate cancer and can be used as a screening method for prostate cancer drug development. 
     
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT  
       [0032]     To identify transcriptional targets downstream of the complex signal transduction pathways of PTEN, we performed a gene expression profiling on prostate cancer and glioblastoma, two cancer types frequently affected by PTEN mutations. This global gene expression analysis identifies a molecular signature that can accurately classify tumor samples according to its PTEN status regardless of tumor types. We also studied IGFBP2, the most significant gene in the signature. We demonstrated that IGFBP2 is biochemically regulated by PTEN and plays a functional role in PTEN function.  
       A. Definitions  
       [0033]     To facilitate understanding of the invention, a number of terms are defined below:  
         [0034]     Nucleotide: a monomeric unit of DNA or RNA consisting of a sugar moiety (pentose), a phosphate, and a nitrogenous heterocyclic base. The base is linked to the sugar moiety via the glycosidic carbon (1′ carbon of the pentose) and that combination of base and sugar is a nucleoside. A nucleoside containing at least one phosphate group bonded to the 3′ or 5′ position of the pentose is a nucleotide.  
         [0035]     Base Pair (bp): a partnership of adenine (A) with thymine (T), or of cytosine (C) with guanine (G) in a double stranded DNA molecule. In RNA, uracil (U) is substituted for thymine. Generally the partnership is achieved through hydrogen bonding.  
         [0036]     Nucleic Acid: a polymer of nucleotides, either single or double stranded.  
         [0037]     Gene: a nucleic acid whose nucleotide sequence codes for an RNA or a polypeptide. A gene can be either RNA or DNA.  
         [0038]     cDNA: a single stranded DNA that is homologous to an MrRNA sequence and does not contain any intronic sequences.  
         [0039]     Sense: a nucleic acid molecule in the same sequence order and composition as the homolog mRNA. The sense conformation is indicated with a “+”, “s” or “sense” symbol.  
         [0040]     Antisense: a nucleic acid molecule complementary to the respective mRNA molecule. The antisense conformation is indicated as a “−” symbol or with a “a” or “antisense” in front of the DNA or RNA, e.g., “aDNA” or “aRNA”.  
         [0041]     Template: a nucleic acid molecule being copied by a nucleic acid polymerase. A template can be single-stranded, double-stranded or partially double-stranded, depending on the polymerase. The synthesized copy is complementary to the template, or to at least one strand of a double-stranded or partially double-stranded template. Both RNA and DNA are synthesized in the 5′ to 3′ direction. The two strands of a nucleic acid duplex are always aligned so that the 5′ ends of the two strands are at opposite ends of the duplex (and, by necessity, so then are the 3′ ends).  
         [0042]     Nucleic Acid Template: a double-stranded DNA molecule, double stranded RNA molecule, hybrid molecules such as DNA-RNA or RNA-DNA hybrid, or single-stranded DNA or RNA molecule.  
         [0043]     Oligonucleotide: a molecule comprised of two or more deoxyribonucleotides or ribonucleotides, preferably more than three, and usually more than ten. The exact size will depend on many factors, which in turn depends on the ultimate function or use of the oligonucleotide. The oligonucleotide may be generated in any manner, including chemical synthesis, DNA replication, reverse transcription, or a combination thereof  
         [0044]     Primer: an oligonucleotide complementary to a template. The primer complexes with the template to yield a primer/template duplex for initiation of synthesis by a DNA polymerase. The primer/template complex is extended during DNA synthesis by the addition of covalently bonded bases linked at the 3′ end, which are complementary to the template. The result is a primer extension product. Virtually all known DNA polymerases (including reverse transcriptases) require complexing of an oligonucleotide to a single-stranded template (“priming”) to initiate DNA synthesis. A primer is selected to be “substantially” or “sufficiently” complementary to a strand of specific sequence of the template. A primer must be sufficiently complementary to hybridize with a template strand for primer elongation to occur. A primer sequence need not reflect the exact sequence of the template. For example, a non-complementary nucleotide fragment may be attached to the 5′ end of the primer, with the remainder of the primer sequence being substantially complementary to the strand. Non-complementary bases or longer sequences can be interspersed into the primer, provided that the primer sequence has sufficient complementarity with the sequence of the template to hybridize and thereby form a template/primer complex for synthesis of the extension product of the primer.  
         [0045]     Complementary or Complementarity or Complementation: used in reference to polynucleotides (i.e., a sequence of nucleotides) related by the base-pairing rules. For example, the sequence “A-G-T” is complementary to the sequence “T-C-A,” and also to “T-C-U.” Complementation can be between two DNA strands, a DNA and an RNA strand, or between two RNA strands. Complementarity may be “partial” or “complete” or “total”. Partial complementarity or complementation occurs when only some of the nucleic acid bases are matched according to the base pairing rules. Complete or total complementarity or complementation occurs when the bases are completely matched between the nucleic acid strands. The degree of complementarity between nucleic acid strands has significant effects on the efficiency and strength of hybridization between nucleic acid strands. This is of particular importance in amplification reactions, as well as in detection methods that depend on binding between nucleic acids. Percent complementarity or complementation refers to the number of mismatch bases over the total bases in one strand of the nucleic acid. Thus, a 50% complementation means that half of the bases were mismatched and half were matched. Two strands of nucleic acid can be complementary even though the two strands differ in the number of bases. In this situation, the complementation occurs between the portion of the longer strand corresponding to the bases on that strand that pair with the bases on the shorter strand.  
         [0046]     Homologous or homology: refers to a polynucleotide sequence having similarities with a gene or mRNA sequence. A nucleic acid sequence may be partially or completely homologous to a particular gene or mRNA sequence, for example. Homology may also be expressed as a percentage determined by the number of similar nucleotides over the total number of nucleotides.  
         [0047]     Complementary Bases: nucleotides that normally pair up when DNA or RNA adopts a double stranded configuration.  
         [0048]     Complementary Nucleotide Sequence: a sequence of nucleotides in a single-stranded molecule of DNA or RNA that is sufficiently complementary to that on another single strand to specifically hybridize between the two strands with consequent hydrogen bonding.  
         [0049]     Conserved: a nucleotide sequence is conserved with respect to a preselected (reference) sequence if it non-randomly hybridizes to an exact or total complement of the preselected sequence.  
         [0050]     Hybridize and Hybridization: the formation of complexes between nucleotide sequences which are sufficiently complementary to form complexes via complementary base pairing. Where a primer (or splice template) “hybridizes” with target (template), such complexes (or hybrids) are sufficiently stable to serve the priming function required by a DNA polymerase to initiate DNA synthesis. There is a specific, i.e. non-random, interaction between two complementary polynucleotide that can be competitively inhibited.  
         [0051]     Nucleotide Analog: a purine or pyrimidine nucleotide that differs structurally from T. G. C, or U, but is sufficiently similar to substitute for the normal nucleotide in a nucleic acid molecule.  
         [0052]     DNA Homolog: a nucleic acid having a preselected conserved nucleotide sequence and a sequence coding for a receptor capable of binding a preselected ligand.  
         [0053]     Amplification: nucleic acid replication involving template specificity. Template specificity is frequently described in terms of “target” specificity. Target sequences are “targets” in that they are sought to be sorted out from other nucleic acids. Amplification techniques have been designed primarily for this sorting. Template specificity is achieved in most amplification techniques by the choice of enzyme.  
         [0054]     Enzymatic Amplification: a method for increasing the concentration of a segment in a target sequence from a mixture of nucleic acids without cloning or purification.  
         [0055]     Polymerase Chain Reaction (PCR): an amplification reaction is typically carried out by cycling i.e., simultaneously performing in one admixture, the first and second primer extension reactions, each cycle comprising polynucleotide synthesis followed by denaturation of the double stranded polynucleotides formed. Methods and systems for amplifying a DNA homolog are described in U.S. Pat. Nos. 4,683,195 and 4,683,202, both to Mullis et al.  
         [0056]     Amplifiable Nucleic Acid and Amplified Products: nucleic acids that may be amplified by any amplification method.  
         [0057]     DNA-dependent DNA Polymerase: an enzyme that synthesizes a complementary DNA copy from a DNA template. Examples are DNA polymerase 1 from  E. coli  and bacteriophage T7 DNA polymerase. Under suitable conditions a DNA-dependent DNA polymerase may synthesize a complementary DNA copy from an RNA template.  
         [0058]     DNA-dependent RNA Polymerase or Transcriptase: enzymes that synthesize multiple RNA copies from a double stranded or partially double stranded DNA molecule having a promoter sequence. Examples of transcriptases include, but are not limited to, DNA-dependent RNA polymerase from  E. coli  and bacteriophage T7, T3, and SP6.  
         [0059]     RNA-dependent DNA Polymerase or Reverse Transcriptase: enzymes that synthesize a complementary DNA copy from an RNA template. All known reverse transcriptases also have the ability to make a complementary DNA copy from a DNA template. Thus, reverse transcriptases are both RNA-dependent and DNA-dependent DNA polymerases.  
         [0060]     RNase H: an enzyme that degrades the RNA portion of an RNA/DNA duplex. RNase H may be an endonuclease or an exonuclease. Most reverse transcriptase enzymes normally contain an RNase H activity. However, other sources of RNase H are available, without an associated polymerase activity. The degradation may result in separation of the RNA from a RNA/DNA complex. Alternatively, the RNase H may simply cut the RNA at various locations such that pieces of the RNA melt off or are susceptible to enzymes that unwind portions of the RNA.  
         [0061]     Reverse Transcription: the synthesis of a DNA molecule from an RNA molecule using an enzymatic reaction in vitro. For example, the RNA molecule may be primed with a primer that is complementary to the RNA molecule and the DNA molecule is synthesized by extension using a reverse transcriptase such as the DNA polymerase with reverse transcription activity, MMLV reverse transcriptase, AMV reverse transcriptase, and any other enzyme that has the ability to synthesize a DNA molecule from an RNA molecule template.  
         [0062]     In Vitro Transcription: the synthesis of an RNA molecule from a DNA molecule using an enzymatic reaction in vitro. For example, the DNA molecule may be double stranded and comprises an RNA polymerase promoter such as T7, SP6, T3, or any other enzyme. promoter for synthesis of RNA from DNA.  
         [0063]     Vector: a recombinant nucleic acid molecule such as recombinant DNA (rDNA) capable of movement and residence in different genetic environments. Generally, another nucleic acid is operatively linked therein. The vector can be capable of autonomous replication in a cell in which case the vector and the attached segment is replicated. One type of preferred vector is an episome, i.e., a nucleic acid molecule capable of extrachromosomal replication. Preferred vectors are those capable of autonomous replication and/or expression of nucleic acids to which they are linked. Vectors capable of directing the expression of genes encoding for one or more polypeptides are referred to herein as “expression vectors”. Particularly important vectors allow cloning of cDNA from mRNAs produced using a reverse transcriptase.  
         [0064]     Functional parts: a portion of an intact molecule that retains one or more desired properties of the intact molecules. Thus, for example, an antibody binds an antigen. In that context of the property of binding that antigen, a functional part of an antibody can be any portion of an antibody that binds the cognate antigen. Similarly, a functional part of a nucleic acid that encodes an antibody that binds that antigen is any portion of that nucleic acid that encodes a polypeptide that binds to that antigen.  
         [0065]     Antibody: in various grammatical forms as used herein refers to immunoglobulin molecules and immunologically active portions of immunoglobulin molecules, i.e., molecules that contain a combining site for antigen or paratope. Exemplary antibody molecules are intact immunoglobulin molecules, substantially intact immunoglobulin molecules and portions of an immunoglobulin molecules, including those portions known in the art as F ab , F ab&#39;s  (F ab′ ) 2 , F v  and scF v .  
         [0066]     Immunoreact: in various forms means specific binding between an antigenic determinant-containing molecule and a molecule containing an antibody combining site such as a whole antibody molecule or a portion thereof.  
         [0067]     Cistron: a sequence of nucleotides in a DNA molecule coding for an amino acid residue sequence and including upstream and downstream DNA expression control elements.  
         [0068]     Promoter: a nucleic acid to which a polymerase molecule recognizes, perhaps binds to, and initiates synthesis. For the purposes of the instant invention, a promoter can be a known polymerase binding site, an enhancer and the like, any sequence that can initiate synthesis by a desired polymerase.  
         [0069]     Knockdown: a method to which a RNA made from a DNA sequence (shRNA) introduced into a cell or a RNA sequence (siRNA) introduced into a cell to initiate degradation of the mRNA of a protein of interest.  
       B. Methods  
       [0070]     The present invention provides a novel method for identifying and selecting genes that associate with PTEN gene abnormalities and/or PTEN-related cellular process, and/or PI3K- and/or Akt-related signal transduction pathway. The present invention combines the following elements as discussed in details thereafter:  
         [0071]     1. isolation of nucleic acids (genomic DNAs or mRNAs) from tumor cells, tumor specimens;  
         [0072]     2.preparation of tumor samples for probing microarrays or gene chips;  
         [0073]     3.performing gene chip hybridization with tumor samples;  
         [0074]     4.Random Forest (RF) computational analyses of the gene chip datasets;  
         [0075]     5. identifying genes with predictive power for association with PTEN status tumor and cancer cells.  
         [0076]     The invention now will be exemplified further in the following non-limiting examples.  
       EXAMPLES  
     Example 1  
     Random Forest Deals Effectively with Microarray Data  
       [0077]     We have used microarray technology to identify overexpression of androgen receptor as the general mechanism for hormone refractory prostate cancer. The data indicate that overexpression of androgen receptor is a diagnostic and therapeutic target for hormone refractory prostate cancer and can be used as a screening method for hormone refractory prostate cancer drug development ( FIG. 7 ). This is consistent with microarray technology being a useful tool for a variety of purposes. However, it has been difficult in identifying molecular signatures for signal transduction pathways. One of the reasons is that microarray experiments are usually performed on a relatively few samples, therefore, data analysis on these experiments requires specific statistical tools. In this report, we described a novel unsupervised learning algorithm, called Random Forest, to identify a molecular signature for the signaling pathway of PTEN. This statistic tool can deal effectively with small data sets involving relatively a few observations (samples) and a large volume of variables (gene expression values). It can calculate a predictive power for each gene. When a set of genes is used to predict the PTEN status, it can also generate an error rate by a three-fold cross-validation, in which one-third of the samples are left out as test set Therefore, identification and verification of signatures, and identification of significant genes can be achieved using this algorithm.  
       Example 2  
     Molecular Signature of the PTEN Tumor Suppressor  
       [0078]     To identify transcriptional targets associate with the PTEN tumor suppressor function, we compared the gene expression profiles of 11 tissue samples that have the wild-type PTEN gene to those of 14 samples that have mutated PTEN gene (table 1). These 25 samples include 12 advanced prostate cancer xenografts and 13 glioblastoma tissue samples. The PTEN status of the prostate cancer xenografts were characterized previously (21) and those of the glioblastoma were determined by western blot and genomic DNA sequence analysis. Six of the glioblastoma samples do not express the PTEN protein and, therefore, were defined as PTEN mutant samples. The other seven samples have the wild-type PTEN because they express the PTEN protein and they do not carry point mutation, which was determined by genomic DNA sequence analysis. We used both prostate cancer and glioblastoma tissue samples in order to increase a tissue-independent signature associated with the PTEN status. We adopted a statistic technique called Random Forest (RF) because this method has been designed to analyze data that contain many covariates and relatively few observations (Breiman L, 1999). This technique is ideal to analyze microarray data, in which expression of a large number of genes is observed in a relatively few samples. This approach identified 490 genes that have statistic power in predicting the PTEN status, and ranked each gene according to the significance of its predictive power, which is represented by Gini index ( FIG. 1A ).  
         [0079]     We next ask how many genes must be included in order to correctly predict the PTEN status, since most of the 490 genes have weak predictive power (their Gini indexes are near zero). We generated an error rate for each gene set by a three-fold cross-validation, in which one-third of the samples were left out as test sets. The first gene in the gene set was the one with the most predictive power (the highest Gini index), and a following gene was added each time according to its ranking of the Gini index. A gene list cannot predict the PTEN status accurately until 12 genes with the highest Gini indexes were included ( FIG. 1B ). The accurate prediction was maintained in gene lists composed of the “top” 18 genes and was lost when more genes were included, consistent with the fact that each gene has different Gini index and, therefore, carries different weights in predicting the PTEN status. The accuracy of the 12 genes to predict the PTEN status in the test set was confirmed by multidimensional scaling analysis ( FIG. 1C ) and by hierarchical clustering ( FIG. 1D ). Glioblastoma and prostate cancer were clustered into PTEN mutant or wild type tumor regardless of cancer types. Further studies are required to determine whether this signature can be exploited more broadly as a tool to define PTEN status of tumors using larger, independent datasets with characterized PTEN status tumors.  
       Example 3  
     Elevated Levels of IGFBP2 Expression in PTEN Mutant Tumors  
       [0080]     Having identified several genes whose expression patterns correlate with the PTEN status, we wish to investigate biochemical regulation and biological role of one of these genes in PTEN function. Because both probe sets in the microarray were identified and both have the highest power in predicting the PTEN status, IGFBP2 was chosen for further study. As the first step, we confirmed the relationship between PTEN mutations and IGFBP2 expression by western blot analysis using whole tissue lysates from prostate cancer xenografts. IGFBP2 protein was detected in PTEN mutated xenografts LAPC9, LUCaP 35, and LNCaP but not in PTEN wild-type tumors LAPC4 and LUCaP23 ( FIG. 2A , table 1), consistent with the microarray analysis.  
         [0081]     The relationship was extended to other tumors that were not included in the microarray analysis. IGFBP2 was highly expressed in PTEN mutated tumors LAPC3, LAPC12, and LUCaP41, but was not detected in PTEN wild-type tumor LAPC14 ( FIG. 2A , table 1). This association also holds true for 23 of the 24 glioblastoma samples examined, of which 13 samples were included in the microarray analysis and 10 of them were independent samples ( FIG. 2B , table 1). IGFBP2 protein was detected in samples whose PTEN expression was low or lost, but was not detected in samples whose PTEN expression was high. Genomic sequence analysis indicate that the PTEN protein detected in the western blot analysis was wild-type. The correlation was confirmed by immunohistochemical analysis (unpublished data, Paul Mischel).  
         [0082]     There is one exception for the association between the PTEN mutations and IGFBP2 expression in glioblastoma samples ( FIG. 2B , table 1). This sample (#429) has PTEN protein expression while IGFBP2 is also highly expressed. Genomic sequence analysis indicates that this sample has the wild-type PTEN gene, suggesting that mechanisms other than PTEN mutations are responsible. Indeed, this sample has high levels of Akt and Akt activation, as indicated by western blot analysis on total Akt and phosphorylation of ser 473 of Akt ( FIG. 2C ). The mechanism of elevated Akt level in this specific patient is unknown.  
         [0083]     To examine if high level of IGFBP2 is secreted by cells with PTEN mutations, glioblastoma (9L and U251) and prostate cancer cells (LAPC4 and LNCaP) were grown in tissue culture and the IGFBP2 levels were measured by radioimmunoassay. In contrast to less than 20 ng/ml of secreted IGFBP2 by cells with wild-type PTEN genes, the levels of secreted protein in cells with mutated PTEN gene are more than 70 ng/ml ( FIG. 2D ). The high levels of secreted IGFBP2 were also detected in PTEN mutated breast cancer cell (MDA-MB-468), but not in PTEN wild-type breast cancer cell (SkBr3).  
         [0084]     To examine if serum IGFBP2 levels correlate with PTEN status in tumors, serum levels of human IGFBP2 were measured from mice carrying human prostate and breast cancer xenografts ( FIG. 2E ). While serum levels of human IGFBP2 levels were low in mice carrying human tumors with the wild-type PTEN genes, mice with PTEN mutated tumors contained high levels of human IGFBP2 in serum. These data indicate that human tumors with PTEN mutations secreted high levels of IGFBP2, and raise the possibility that serum IGFBP-2 levels could serve as a biomarker for PTEN status.  
       Example 4  
     Inhibition of IGFBP2 Expression by PTEN  
       [0085]     To establish a causal role of PTEN loss in IGFBP-2 upregulation, we extended our analysis to an isogenic model. Western blot analysis was performed using the lysates from the PTEN wild-type and deleted isogenic mouse embryonic fibroblasts (MEF) (22). While IGFBP2 protein was barely detectable in PTEN wild-type MEF, PTEN mutant cells produced a high level of IGFBP2 ( FIG. 3A ).  
         [0086]     To determine if upregulation of the IGFBP2 expression by the PTEN mutations is dependent upon the PI3K/Akt pathway, pharmacological and genetic approaches were employed. When PTEN mutated cells were treated with a pharmacological drug (LY294002) that inhibits the PI3K kinase activity, the production of IGFBP2 was reduced to the basal level ( FIG. 3B ). Furthermore, IGFBP2 was induced in cells with the wild-type PTEN gene when a constitutively active Akt allele was expressed ( FIG. 3C ). These results indicate that IGFBP2 expression is induced by the PI3K/Akt pathway, which is antagonized by the PTEN tumor suppressor.  
       Example 5  
     Functional Role of IGFBP2 in the PTEN/Akt Signaling  
       [0087]     To determine if IGFBP2 plays a functional role in the PTEN signal transduction pathway, we introduced either PTEN or IGFBP-2 into PTEN null cell lines by lentiviral infection, which gives highly efficient infection rates in prostate cancer epithelial cells (&gt;90%). As reported, re-introduction of the wild-type PTEN decreased growth of PC3 cells by 36% ( FIG. 4A ), with a concomitant decrease of the endogenous IGFBP2 expression ( FIG. 4C ). Forced expression of exogenous IGFBP2 rescued the growth inhibition of PTEN by 47% ( FIG. 4A ). A similar effect was observed with cell cycle analysis ( FIG. 4B ). Re-introduction of the wild-type PTEN into PC3 cell reduced the percentage of cells in S phase, and the effect is partially rescued by forced expression of exogenous IGFBP2. These data suggest that down-regulation of IGFBP2 may partially contribute to the PTEN tumor suppressor function.  
         [0088]     To examine if IGFBP2 is involved in the PI3K signaling, a pharmacological approach was employed. Consistent with the result in  FIG. 3B , LNCaP cells have a high basal level of Akt activation. Treatment of LY294002, a specific PI3K inhibitor, resulted in reduced Akt phosphorylation and IGFBP2 expression ( FIG. 5A , bottom panel). This treatment caused a decrease of the percentage of cells in S phase by 40%, and the reduction was partially (28%) rescued by the forced expression of exogenous IGFBP2 ( FIG. 5A , top panel). To examine if IGFBP2 plays a biological role for Akt function, clonogenic assay was performed using IGFBP2 knockout MEF (23). While Akt promoted colony formation in IGFBP2 wild type MEF ( FIG. 5B , top and left panel), deletion of IGFBP2 abrogated this promoting activity. The requirement of IGFBP2 is specific to Akt because c-myc promoted colony formation in both cells ( FIG. 5C ). The inability of Akt to promote colony formation in IGFBP2 knockout MEF can be rescued by re-introduction of IGFBP2 ( FIG. 5B ). Taken together, these results indicate that one of the effects of the PTEN tumor suppressor is to suppress the expression of IGFBP2, which is involved in the function of the PI3K/Akt signal transduction pathway.  
         [0089]     To determine how IGFBP2 is involved in Akt function, we made use of gene knockdown technology by shRNA. The shRNA efficiently knockdown IGFBP2 expression, as shown by western blot analysis ( FIG. 6 ). This knockdown reduced the growth of PC3 and the activation of Akt, effects identical to re-introduction of the wild-type PTEN ( FIG. 6 ). These data suggest that IGFBP2 may regulate Akt activation through an autoloop mechanism.  
       Example 6  
     IGFBP2 is a Surrogate Marker for PTEN  
       [0090]     Through random forest and other statistical analysis, we identified upregulation of IGFBP2 expression as the most consistent change associated with PTEN mutations. Among 12559 probe sets in the microarray, both probe sets representing IGFBP2 were identified as the most and the second most significant gene to predict the PTEN status. We demonstrated that IGFBP2 is biochemically regulated by PTEN and PI3K-Akt pathway. Consistent with our finding, it was reported that overexpression of IGFBP2 was only observed in glioblastoma, but not in low- or intermediate-grade gliomas (24). In addition, IGFBP2 overexpression was observed in 50% of glioblastoma. The stage in which IGFBP2 is overexpressed and the percentage of tumors with this gene overexpression coincide with the frequency of PTEN mutations in advanced gliomas (25). Overexpression of IGFBP2 was also identified as the most distinct progression-related expression change in high-grade gliomas in another similar study through cDNA microarrays and tissue arrays (26). This study uncovered that IGFBP2 is a poor prognostic marker for patients with gliomas. While patients with IGFBP2 negative tumors had a mean survival of 75 months, patients with tumors of strong IGFBP2 expression had a mean survival of 23 months. This also coincides with the aggressiveness of PTEN mutated tumors. These data suggest that upregulation of IGFBP2 in PTEN mutated tumors may play an important role in tumor formation and progression. Indeed, forced expression of IGFBP2 partially rescued the inhibitory effect of PTEN and a PI3K inhibitor as well ( FIG. 4 ).  
       Example 7  
     Serum IGFBP2 can be Developed as a Surrogate Marker for PTEN Mutations and Akt Activation  
       [0091]     We and other have recently demonstrated that tumors with PTEN mutations are more sensitive to drugs such as CCI-779 that targets mTOR, a downstream effector of the PI3K/Akt pathway (22, 27). This effect is later observed in several other studies. These studies suggest that drugs targeting the PI3K/Alkt pathway may only benefit patients who have aberrant PTEN/Akt activities. Since PTEN mutations are carried in less than 50% of tumors even for the most frequently mutated cancer type, the pharmaceutical benefit can be masked by an unselected population. This may explain why CCI-779 and some other drugs targeting the PI3K-Akt pathway fail in clinical trials, even though this drug effectively inhibits PTEN mutated cancer cells. Because IGFBP2 is a serum protein, we envision that the serum level of IGFBP2 can be used to predict PTEN mutations and Akt activation. In support of this notion, we detected high concentrations of human IGFBP2 in condition medium of PTEN mutated cells and also in sera of mice carrying PTEN mutated human tumors. In addition, serum concentration of IGFBP2 was shown to be elevated in 50% of patients with advanced prostate cancer (personal communication, Pinchas Cohen). The stage in which IGFBP2 is overexpressed and the percentage of tumors with this gene overexpression coincide with the frequency of PTEN mutations in advanced prostate cancer in patients. Furthermore, it was reported that patients treated with IGF-l, a stimulus for Akt activation, caused an elevated level of IGFBP2 in serum (28). Serum level of IGFBP2 can also be used to predict if drugs hit targets because overexpression of IGFBP2 can be inhibited by a PI3K inhibitor.  
       Example 8  
     Potential Downstream Targets of PTEN  
       [0092]     The smallest gene expression signature associated with the PTEN status contained eight down-regulated and four up-regulated genes in PTEN mutated tumors ( FIG. 1D ). Several of the identified genes were involved in different pathways implicated in tumor formation and progression. Human neuralized belongs to a family of the neurogenic genes and is an E3 ligase for the Notch signal transduction pathway that is associated with tumorigenesis (29, 30). This protein mediates proteosome-dependent degradation of the Notch ligand Delta (31). Loss-of-function mutations of the neurogenic genes produce hyperplasia of the embryonic nervous system (32), which is reminiscent of phenotype of the brain-specific PTEN knockout mice (33). Furthermore, expression of human neuralized is high in normal human brain tissue, but low or absent in advanced gliomas (34), consistent with our finding. These data suggest that the notch pathway may play an important role in PTEN tumor suppressor function. Dual specificity phosphatase 10, also called MKP-5, selectively dephosphorylates JNK and reduces its activity (35). The level of this phosphatase is reduced in tumors with PTEN loss, suggesting that upregulation of the JNK signal transduction pathway is a key element for cancer development and progression in PTEN-null tumors. This hypothesis is supported by our unpublished data. Curiously, two proteins identified in the signature specifically bind PIP3 (36, 37), the established substrate for the PTEN tumor suppressor. Cytohesin-l belongs to a family of guanine nucleotide-exchange proteins for the 20-kDa ADP ribosylation factor (ARF) (38). It also associates with integrin beta2 and regulate cell adhesion that is important for tumorigenesis and cancer metastasis (39). Regulator of G-protein signaling 1 belongs to a family of GTPase-activating protein and is inhibited by PIP3 (37). These data suggest that a feedback control may be invoked to maintain the PI3K signaling, consistent with a published report that expression of PTEN causes feedback upregulation of IRS-2 (40). Our data suggest that these molecules, particularly these 12 molecules identified through microarray analysis, can be diagnostic and therapeutic targets for PTEN mutated tumors. Current efforts are directed to understand the involvement of these molecules in PTEN tumor suppressor function.  
       References  
       [0093]     All references cited herein and herein incorporated by reference in entirety. Breiman, L. Random forests-random features. Technical Report 567, Department of Statistics, University of California, Berkeley, September 1999.  
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         [0134]     This application is related to U.S. Pat. No. 10/701,490, filed Nov. 5, 2003, the entire contents of which are incorporated herein by reference. Throughout this application, various publications are referenced. The disclosures of these publications are hereby incorporated by reference herein in their entireties.  
                                                                                                                     TABLE 1                       Supplementary Table 1. Validation of the inversed relationship between IGFBP-2       expression and the PTEN mutation in tumors                   Samples in microarray analysis            IGFBP2   IGFBP2       expression   expression            Prostate   RNA (1)   Protein (2)   PTEN status   GBM   RNA   Protein   PTEN status                3    354   no   Wildtype    10   14942   no   Wildtype        4   1807   no   Wildtype    68    655   no   Wildtype        9   1402   no   Wildtype   317    3749   no   Wildtype       10   1131   no   Wildtype   476   16483   no   Wildtype        5   3364   +   Mutant   494   10699   no   Wildtype        6   10861   +   Mutant   502   19414   low   Wildtype       11   7770   +++   Mutant   580    9131   no   Wildtype       12   11237    +++   Mutant    46   37265   +   Mutant       58   11063    ++   Mutant   110   22298   +++   Mutant       62   17217    ++   Mutant   188   48838   +++   Mutant       64   8378   ++   Mutant   203   38755   +   Mutant       65   4695   ++   Mutant   263   35151   ++   Mutant                       268   42889   +++   Mutant                    Samples not included in microarray analysis                IGFBP2 expression       IGFBP2 expression                    Prostate   Protein   PTEN status   GBM   Protein   PTEN status                       LAPC14   no   Wildtype    64   no   Wildtype           LAPC3   +++++   Mutant   103   no   Wildtype           LAPC12   ++++   Mutant   125   no   Wildtype           LuCaP41   ++   Mutant   155   no   Wildtype                       208   no   Wildtype                       305   no   Wildtype                       429   +++   Wildtype                       437   no   Wildtype                        22   +++++   Mutant                       127   ++   Mutant                       202   +++   Mutant                      
 
         [0135]    
       
         
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                 TABLE 2 
               
             
             
               
                   
               
               
                   
               
               
                 Supplementary Table 2. A list of 490 genes with statistic powers in predicting the PTEN status 
               
             
          
           
               
                 Rank 
                 ProbeSet 
                 Gene name 
                 Gini Index 
               
               
                   
               
             
          
           
               
                 1 
                 40422_at 
                 insulin-like growth factor binding protein 2 (36 kD) 
                 1.39 
               
               
                 2 
                 1741_s_at 
                 “S37730/FEATURE = cds/DEFINITION = S37712S4 insulin-like growth factor binding protein- 
                 0.87 
               
               
                   
                   
                 2 [human, placenta, Genomic, 1342 nt, segment 4 of 4]” 
               
               
                 3 
                 40026_g_at 
                 hypothetical protein 
                 0.68 
               
               
                 4 
                 36061_at 
                 Cluster Incl. AF009314:  Homo sapiens  clone TUA8 Cri-du-chat region mRNA/ 
                 0.28 
               
               
                   
                   
                 cds = UNKNOWN/gb = AF009314/gi = 2331117/ug = Hs.49476/len = 1463 
               
               
                 5 
                 38555_at 
                 dual specificity phosphatase 10 
                 0.24 
               
               
                 6 
                 32717_at 
                 neuralized ( Drosophila )-like 
                 0.23 
               
               
                 7 
                 36575_at 
                 regulator of G-protein signalling 1 
                 0.17 
               
               
                 8 
                 32116_at 
                 expressed in activated T/LAK lymphocytes 
                 0.16 
               
               
                 9 
                 39918_at 
                 gamma-tubulin complex protein 2 
                 0.15 
               
               
                 10 
                 38463_s_at 
                 “Cluster Incl. U29926: Human AMP deaminase (AMPD3) gene, promoter 1a region/ 
                 0.14 
               
               
                   
                   
                 cds = (453,2777)/gb = U29926/gi = 1002661/ug = Hs.83918/len = 4018” 
               
               
                 11 
                 36502_at 
                 PFTAIRE protein kinase 1 
                 0.14 
               
               
                 12 
                 38666_at 
                 “pleckstrin homology, Sec7 and coiled/coil domains 1(cytohesin 1)” 
                 0.12 
               
               
                 13 
                 37055_at 
                 ets variant gene 1 
                 0.1 
               
               
                 14 
                 38812_at 
                 “laminin, beta 2 (laminin S)” 
                 0.1 
               
               
                 15 
                 35414_s_at 
                 jagged 1 (Alagille syndrome) 
                 0.1 
               
               
                 16 
                 33807_at 
                 phosphoinositol 3-phosphate-binding protein-2 
                 0.1 
               
               
                 17 
                 38415_at 
                 “protein tyrosine phosphatase type IVA, member 2” 
                 0.09 
               
               
                 18 
                 34993_at 
                 “sarcoglycan, delta (35 kD dystrophin-associated glycoprotein)” 
                 0.08 
               
               
                 19 
                 40971_at 
                 KIAA0229 protein 
                 0.07 
               
               
                 20 
                 1398_g_at 
                 mitogen-activated protein kinase kinase kinase 11 
                 0.07 
               
               
                 21 
                 36935_at 
                 RAS p21 protein activator (GTPase activating protein) 1 
                 0.07 
               
               
                 22 
                 885_g_at 
                 “integrin, alpha 3 (antigen CD49C, alpha 3 subunit of VLA-3 receptor)” 
                 0.07 
               
               
                 23 
                 35275_at 
                 “adaptor-related protein complex 1, gamma 1 subunit” 
                 0.06 
               
               
                 24 
                 40866_at 
                 “NIPSNAP,  C. elegans , homolog 1” 
                 0.06 
               
               
                 25 
                 1506_at 
                 “interleukin 2 receptor, gamma (severe combined immunodeficiency)” 
                 0.06 
               
               
                 26 
                 1910_s_at 
                 B-cell CLL/lymphoma 2 
                 0.06 
               
               
                 27 
                 36212_at 
                 Cluster Incl. AL049218:  Homo sapiens  mRNA; cDNA DKFZp564I1916 (from clone 
                 0.06 
               
               
                   
                   
                 DKFZp564I1916)/cds = UNKNOWN/gb = AL049218/gi = 4499947/ug = Hs.234793/len = 1474 
               
               
                 28 
                 31530_at 
                 acetyl-Coenzyme A carboxylase beta 
                 0.06 
               
               
                 29 
                 37276_at 
                 IQ motif containing GTPase activating protein 2 
                 0.05 
               
               
                 30 
                 41028_at 
                 ryanodine receptor 3 
                 0.05 
               
               
                 31 
                 38336_at 
                 KIAA1013 protein 
                 0.05 
               
               
                 32 
                 1060_g_at 
                 “neurotrophic tyrosine kinase, receptor, type 3” 
                 0.05 
               
               
                 33 
                 37432_g_at 
                 Protein inhibitor of activated STAT X 
                 0.05 
               
               
                 34 
                 34348_at 
                 “serine protease inhibitor, Kunitz type, 2” 
                 0.05 
               
               
                 35 
                 884_at 
                 “integrin, alpha 3 (antigen CD49C, alpha 3 subunit of VLA-3 receptor)” 
                 0.05 
               
               
                 36 
                 33453_at 
                 “ATPase, H+ transporting, lysosomal (vacuolar proton pump), subunit 1” 
                 0.05 
               
               
                 37 
                 36659_at 
                 “collagen, type IV, alpha 2” 
                 0.05 
               
               
                 38 
                 38110_at 
                 syndecan binding protein (syntenin) 
                 0.05 
               
               
                 39 
                 41385_at 
                 erythrocyte membrane protein band 4.1-like 3 
                 0.05 
               
               
                 40 
                 41176_at 
                 hypothetical protein FLJ12443 
                 0.05 
               
               
                 41 
                 32174_at 
                 “solute carrier family 9 (sodium/hydrogen exchanger), isoform 3 regulatory factor 1” 
                 0.05 
               
               
                 42 
                 32571_at 
                 “methionine adenosyltransferase II, alpha” 
                 0.05 
               
               
                 43 
                 40935_at 
                 hypothetical protein MGC11308 
                 0.04 
               
               
                 44 
                 39391_at 
                 associated molecule with the SH3 domain of STAM 
                 0.04 
               
               
                 45 
                 232_at 
                 “M55210/FEATURE = mRNA#1/DEFINITION = HUMLB2A26 Human laminin B2 chain gene, 
                 0.04 
               
               
                   
                   
                 exon 28” 
               
               
                 46 
                 38650_at 
                 Cluster Incl. L27560: Human insulin-like growth factor binding protein 5 (IGFBP5) mRNA/ 
                 0.04 
               
               
                   
                   
                 cds = UNKNOWN/gb = L27560/gi = 452059/ug = Hs.103391/len = 3658 
               
               
                 47 
                 34508_r_at 
                 KIAA1079 protein 
                 0.04 
               
               
                 48 
                 41789_r_at 
                 KIAA0669 gene product 
                 0.04 
               
               
                 49 
                 41132_r_at 
                 heterogeneous nuclear ribonucleoprotein H2 (H‘) 
                 0.04 
               
               
                 50 
                 40210_at 
                 “RAB13, member RAS oncogene family” 
                 0.03 
               
               
                 51 
                 1293_s_at 
                 glycosylphosphatidylinositol specific phospholipase D1 
                 0.03 
               
               
                 52 
                 39174_at 
                 nuclear receptor coactivator 4 
                 0.03 
               
               
                 53 
                 37640_at 
                 hypoxanthine phosphoribosyltransferase 1 (Lesch-Nyhan syndrome) 
                 0.03 
               
               
                 54 
                 1287_at 
                 ADP-ribosyltransferase (NAD+; poly (ADP-ribose) polymerase) 
                 0.03 
               
               
                 55 
                 39082_at 
                 annexin A6 
                 0.03 
               
               
                 56 
                 35247_at 
                 “small nuclear RNA activating complex, polypeptide 5, 19 kD” 
                 0.03 
               
               
                 57 
                 39797_at 
                 KIAA0349 protein 
                 0.03 
               
               
                 58 
                 39550_at 
                 chromosome 1 open reading frame 17 
                 0.03 
               
               
                 59 
                 33993_at 
                 “myosin, light polypeptide 6, alkali, smooth muscle and non-muscle” 
                 0.03 
               
               
                 60 
                 38030_at 
                 KIAA0332 protein 
                 0.03 
               
               
                 61 
                 410_s_at 
                 “casein kinase 2, beta polypeptide” 
                 0.03 
               
               
                 62 
                 153_f_at 
                 “H2B histone family, member R” 
                 0.03 
               
               
                 63 
                 32695_at 
                 bombesin-like receptor 3 
                 0.03 
               
               
                 64 
                 33050_at 
                 dopamine receptor D5 
                 0.03 
               
               
                 65 
                 40399_r_at 
                 mesenchyme homeo box 2 (growth arrest-specific homeo box) 
                 0.03 
               
               
                 66 
                 1434_at 
                 phosphatase and tensin homolog (mutated in multiple advanced cancers 1) 
                 0.03 
               
               
                 67 
                 41035_at 
                 KIAA0775 gene product 
                 0.03 
               
               
                 68 
                 1535_at 
                 checkpoint suppressor 1 
                 0.03 
               
               
                 69 
                 32769_at 
                 KIAA0993 protein 
                 0.02 
               
               
                 70 
                 33155_at 
                 “Cluster Incl. M95740: Human alpha-L-iduronidase gene/cds = (0.1961)/gb = M95740/ 
                 0.02 
               
               
                   
                   
                 gi = 178412/ug = Hs.89560/len = 2234” 
               
               
                 71 
                 38769_at 
                 a disintegrin and metalloproteinase domain 12 (meltrin alpha) 
                 0.02 
               
               
                 72 
                 491_at 
                 “U46116/FEATURE = mRNA/DEFINITION = HSPTPRG28 Human receptor tyrosine 
                 0.02 
               
               
                   
                   
                 phosphatase gamma (PTPRG) gene, exon 30 and complete cds” 
               
               
                 73 
                 34397_at 
                 acid-inducible phosphoprotein 
                 0.02 
               
               
                 74 
                 41131_f_at 
                 heterogeneous nuclear ribonucleoprotein H2 (H‘) 
                 0.02 
               
               
                 75 
                 31995_g_at 
                 brefeldin A-inhibited guanine nucleotide-exchange protein 2 
                 0.02 
               
               
                 76 
                 1346_at 
                 metallothionein 3 (growth inhibitory factor (neurotrophic)) 
                 0.02 
               
               
                 77 
                 36672_at 
                 prolylcarboxypeptidase (angiotensinase C) 
                 0.02 
               
               
                 78 
                 36188_at 
                 general transcription factor IIIA 
                 0.02 
               
               
                 79 
                 31773_at 
                 cytochrome b-561 
                 0.02 
               
               
                 80 
                 40504_at 
                 paraoxonase 2 
                 0.02 
               
               
                 81 
                 41277_at 
                 “sin3-associated polypeptide, 18 kD” 
                 0.02 
               
               
                 82 
                 35239_at 
                 emerin (Emery-Dreifuss muscular dystrophy) 
                 0.02 
               
               
                 83 
                 32774_at 
                 “NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 8 (19 kD, ASHI)” 
                 0.02 
               
               
                 84 
                 39993_at 
                 “phosphatidylinositol glycan, class A (paroxysmal nocturnal hemoglobinuria)” 
                 0.02 
               
               
                 85 
                 41693_r_at 
                 carnitine O-octanoyltransferase 
                 0.02 
               
               
                 86 
                 41866_s_at 
                 “dystrobrevin, beta” 
                 0.02 
               
               
                 87 
                 38607_at 
                 transmembrane 4 superfamily member 5 
                 0.02 
               
               
                 88 
                 41431_at 
                 MAK-related kinase 
                 0.02 
               
               
                 89 
                 38264_at 
                 RAB interacting factor 
                 0.02 
               
               
                 90 
                 1396_at 
                 L27560/FEATURE = mRNA/DEFINITION = HUMIGFBP5X Human insulin-like growth factor 
                 0.02 
               
               
                   
                   
                 binding protein 5 (IGFBP5) mRNA 
               
               
                 91 
                 40792_s_at 
                 triple functional domain (PTPRF interacting) 
                 0.02 
               
               
                 92 
                 37511_at 
                 B9 protein 
                 0.02 
               
               
                 93 
                 41814_at 
                 “fucosidase, alpha-L-1, tissue” 
                 0.02 
               
               
                 94 
                 37998_at 
                 superkiller viralicidic activity 2 ( S. cerevisiae  homolog)-like 
                 0.02 
               
               
                 95 
                 32059_at 
                 Cluster Incl. U79282: Human clone 23801 mRNA sequence/cds = UNKNOWN/gb = U79282/ 
                 0.02 
               
               
                   
                   
                 gi = 1710254/ug = Hs.155572/len = 1694 
               
               
                 96 
                 39134_at 
                 target of myb1 (chicken) homolog 
                 0.02 
               
               
                 97 
                 35148_at 
                 “amyloid beta (A4) precursor protein-binding, family A, member 3 (X11-like 2)” 
                 0.02 
               
               
                 98 
                 1804_at 
                 “kallikrein 3, (prostate specific antigen)” 
                 0.02 
               
               
                 99 
                 719_g_at 
                 “protease, serine, 11 (IGF binding)” 
                 0.02 
               
               
                 100 
                 32642_at 
                 chondroitin sulfate proteoglycan 3 (neurocan) 
                 0.02 
               
               
                 101 
                 38096_f_at 
                 “major histocompatibility complex, class II, DP beta 1” 
                 0.02 
               
               
                 102 
                 41124_r_at 
                 ectonucleotide pyrophosphatase/phosphodiesterase 2 (autotaxin) 
                 0.02 
               
               
                 103 
                 36444_s_at 
                 “small inducible cytokine subfamily A (Cys-Cys), member 16” 
                 0.02 
               
               
                 104 
                 41256_at 
                 eukaryotic translation elongation factor 1 delta (guanine nucleotide exchange protein) 
                 0.02 
               
               
                 105 
                 31418_at 
                 high-mobility group (nonhistone chromosomal) protein 17-like 1 
                 0.02 
               
               
                 106 
                 40679_at 
                 “solute carrier family 6 (neurotransmitter transporter, betaine/GABA), member 12” 
                 0.02 
               
               
                 107 
                 172_at 
                 “inositol polyphosphate-5-phosphatase, 145 kD” 
                 0.02 
               
               
                 108 
                 41308_at 
                 C-terminal binding protein 1 
                 0.02 
               
               
                 109 
                 41238_s_at 
                 “Cluster Incl. M18700: Human elastase III A gene/cds = (18,827)/gb = M18700/gi = 806625/ 
                 0.02 
               
               
                   
                   
                 ug = Hs.181289/len = 918” 
               
               
                 110 
                 32264_at 
                 granzyme M (lymphocyte met-ase 1) 
                 0.02 
               
               
                 111 
                 1779_s_at 
                 pim-1 oncogene 
                 0.02 
               
               
                 112 
                 39778_at 
                 “mannosyl (alpha-1,3-)-glycoprotein beta-1,2-N-acetylglucosaminyltransferase” 
                 0.02 
               
               
                 113 
                 1579_at 
                 “M27288/FEATURE = cds/DEFINITION = HUMOCS3 Human oncostatin M gene, exon 3” 
                 0.02 
               
               
                 114 
                 38043_at 
                 2.19 gene 
                 0.02 
               
               
                 115 
                 33712_at 
                 “sulfortranferase family 4A, member 1” 
                 0.02 
               
               
                 116 
                 32918_at 
                 Cluster Incl. AL080182:  Homo sapiens  mRNA; cDNA DKFZp434O151 (from clone 
                 0.02 
               
               
                   
                   
                 DKFZp434O151)/cds = UNKNOWN/gb = AL080182/gi = 5262658/ug = Hs.225129/len = 1454 
               
               
                 117 
                 35155_at 
                 “casein kinase 1, gamma 2” 
                 0.02 
               
               
                 118 
                 1977_s_at 
                 v-ets avian erythroblastosis virus E26 oncogene homolog 1 
                 0.02 
               
               
                 119 
                 34147_g_at 
                 8-oxoguanine DNA glycosylase 
                 0.02 
               
               
                 120 
                 41525_at 
                 high-mobility group 20B 
                 0.02 
               
               
                 121 
                 32068_at 
                 complement component 3a receptor 1 
                 0.02 
               
               
                 122 
                 37331_g_at 
                 “aldehyde dehydrogenase 4 family, member A1” 
                 0.02 
               
               
                 123 
                 39017_at 
                 Lsm1 protein 
                 0.02 
               
               
                 124 
                 34435_at 
                 aquaporin 9 
                 0.02 
               
               
                 125 
                 35939_s_at 
                 “POU domain, class 4, transcription factor 1” 
                 0.02 
               
               
                 126 
                 34226_at 
                 mitogen-activated protein kinase kinase kinase kinase 5 
                 0.02 
               
               
                 127 
                 39602_at 
                 DKFZP586F1018 protein 
                 0.02 
               
               
                 128 
                 33576_at 
                 KIAA0918 protein 
                 0.02 
               
               
                 129 
                 1569_r_at 
                 “L42243/FEATURE = exon#3/DEFINITION = HUMIFNAM08  Homo sapiens  (clone 51H8) 
                 0.02 
               
               
                   
                   
                 alternatively spliced interferon receptor (IFNAR2) gene, exon 9 and complete cds s” 
               
               
                 130 
                 34916_s_at 
                 “tumor necrosis factor receptor superfamily, member 4” 
                 0.02 
               
               
                 131 
                 38696_at 
                 CGG triplet repeat binding protein 1 
                 0.02 
               
               
                 132 
                 37964_at 
                 ring finger protein 3 
                 0.01 
               
               
                 133 
                 32598_at 
                 nel (chicken)-like 2 
                 0.01 
               
               
                 134 
                 36603_at 
                 “GCN1 (general control of amino-acid synthesis 1, yeast)-like 1” 
                 0.01 
               
               
                 135 
                 37737_at 
                 protein-L-isoaspartate (D-aspartate) O-methyltransferase 
                 0.01 
               
               
                 136 
                 36097_at 
                 immediate early protein 
                 0.01 
               
               
                 137 
                 36781_at 
                 “serine (or cysteine) proteinase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 1” 
                 0.01 
               
               
                 138 
                 36919_r_at 
                 formyl peptide receptor 1 
                 0.01 
               
               
                 139 
                 32963_s_at 
                 Rag D protein 
                 0.01 
               
               
                 140 
                 41409_at 
                 basement membrane-induced gene 
                 0.01 
               
               
                 141 
                 36529_at 
                 hypothetical protein MGC2650 
                 0.01 
               
               
                 142 
                 41526_at 
                 high-mobility group 20B 
                 0.01 
               
               
                 143 
                 40004_at 
                 sine oculis homeobox ( Drosophila ) homolog 1 
                 0.01 
               
               
                 144 
                 41858_at 
                 FGF receptor activating protein 1 
                 0.01 
               
               
                 145 
                 40270_at 
                 cell division cycle 2-like 5 (cholinesterase-related cell division controller) 
                 0.01 
               
               
                 146 
                 38606_at 
                 “tryptophan 2,3-dioxygenase” 
                 0.01 
               
               
                 147 
                 41758_at 
                 chromosome 22 open reading frame 5 
                 0.01 
               
               
                 148 
                 36093_at 
                 KIAA0614 protein 
                 0.01 
               
               
                 149 
                 33161_at 
                 “integrin, beta 1 (fibronectin receptor, beta polypeptide, antigen CD29 includes MDF2, 
                 0.01 
               
               
                   
                   
                 MSK12)” 
               
               
                 150 
                 1028_at 
                 “U43431/FEATURE=/DEFINITION = HSU43431 Human DNA topoisomerase III mRNA, 
                 0.01 
               
               
                   
                   
                 complete cds” 
               
               
                 151 
                 1557_at 
                 p21/Cdc42/Rac1-activated kinase 1 (yeast Ste20-related) 
                 0.01 
               
               
                 152 
                 32736_at 
                 HSPC022 protein 
                 0.01 
               
               
                 153 
                 34654_at 
                 myotubularin related protein 1 
                 0.01 
               
               
                 154 
                 39768_at 
                 “Cluster Incl. D13146:  Homo sapiens  gene for 2,3-cyclic-nucleotide 3-phosphodiesterase/ 
                 0.01 
               
               
                   
                   
                 cds = (90,1355)/gb = D13146/gi = 219399/ug = Hs.150741/len = 2594” 
               
               
                 155 
                 40424_at 
                 proline synthetase co-transcribed (bacterial homolog) 
                 0.01 
               
               
                 156 
                 524_at 
                 postmeiotic segregation increased ( S. cerevisiae ) 1 
                 0.01 
               
               
                 157 
                 36125_s_at 
                 RNA-binding protein (autoantigenic) 
                 0.01 
               
               
                 158 
                 857_at 
                 “protein phosphatase 1A (formerly 2C), magnesium-dependent, alpha isoform” 
                 0.01 
               
               
                 159 
                 36833_at 
                 Bruton agammaglobulinemia tyrosine kinase 
                 0.01 
               
               
                 160 
                 40464_g_at 
                 karyopherin (importin) beta 2 
                 0.01 
               
               
                 161 
                 39965_at 
                 “ras-related C3 botulinum toxin substrate 3 (rho family, small GTP binding protein Rac3)” 
                 0.01 
               
               
                 162 
                 38458_at 
                 “Cluster Incl. L39945: Human cytochrome b5 (CYB5) gene/cds = (120,548)/gb = L39945/ 
                 0.01 
               
               
                   
                   
                 gi = 703082/ug = Hs.83834/len = 836” 
               
               
                 163 
                 37748_at 
                 KIAA0232 gene product 
                 0.01 
               
               
                 164 
                 40454_at 
                 FAT tumor suppressor ( Drosophila ) homolog 
                 0.01 
               
               
                 165 
                 34740_at 
                 forkhead box O3A 
                 0.01 
               
               
                 166 
                 36011_at 
                 syntaxin 10 
                 0.01 
               
               
                 167 
                 37568_at 
                 Cluster Incl. U79242: Human clone 23560 mRNA sequence/cds = UNKNOWN/gb = U79242/ 
                 0.01 
               
               
                   
                   
                 gi = 1710189/ug = Hs.79981/len = 1614 
               
               
                 168 
                 40229_at 
                 target of myb1 (chicken) homolog-like 1 
                 0.01 
               
               
                 169 
                 37838_at 
                 coagulation factor XII (Hageman factor) 
                 0.01 
               
               
                 170 
                 1128_s_at 
                 chemokine (C—C motif) receptor 1 
                 0.01 
               
               
                 171 
                 33798_at 
                 KIAA0732 protein 
                 0.01 
               
               
                 172 
                 31728_at 
                 “major histocompatibility complex, class II, DN alpha” 
                 0.01 
               
               
                 173 
                 38947_at 
                 “protein phosphatase, EF hand calcium-binding domain 1” 
                 0.01 
               
               
                 174 
                 1993_s_at 
                 “breast cancer 1, early onset” 
                 0.01 
               
               
                 175 
                 35951_at 
                 neurexin 3 
                 0.01 
               
               
                 176 
                 35642_at 
                 metaxin 2 
                 0.01 
               
               
                 177 
                 32061_at 
                 hypothetical protein FLJ10871 
                 0.01 
               
               
                 178 
                 40195_at 
                 “H2A histone family, member X” 
                 0.01 
               
               
                 179 
                 121_at 
                 paired box gene 8 
                 0.01 
               
               
                 180 
                 40446_at 
                 divalent cation tolerant protein CUTA 
                 0.01 
               
               
                 181 
                 38642_at 
                 activated leucocyte cell adhesion molecule 
                 0.01 
               
               
                 182 
                 33293_at 
                 lifeguard 
                 0.01 
               
               
                 183 
                 35575_f_at 
                 zinc finger protein 253 
                 0.01 
               
               
                 184 
                 38595_r_at 
                 KIAA0284 protein 
                 0.01 
               
               
                 185 
                 833_at 
                 “U40279/FEATURE = cds/DEFINITION = HSITGAD06 Human beta-2 integrin alphaD subunit 
                 0.01 
               
               
                   
                   
                 (ITGAD) gene, exons 25-30, and partial cds” 
               
               
                 186 
                 1675_at 
                 RAS p21 protein activator (GTPase activating protein) 1 
                 0.01 
               
               
                 187 
                 1519_at 
                 v-ets avian erythroblastosis virus E26 oncogene homolog 2 
                 0.01 
               
               
                 188 
                 32172_at 
                 SMART/HDAC1 associated repressor protein 
                 0.01 
               
               
                 189 
                 37480_at 
                 “thrombopoietin (myeloproliferative leukemia virus oncogene ligand, megakaryocyte growth 
                 0.01 
               
               
                   
                   
                 and development factor)” 
               
               
                 190 
                 39940_at 
                 Cluster Incl. AL080094:  Homo sapiens  mRNA; cDNA DKFZp564O1262 (from clone 
                 0.01 
               
               
                   
                   
                 DKFZp564O1262)/cds = UNKNOWN/gb = AL080094/gi = 5262515/ug = Hs.41185/len = 1062 
               
               
                 191 
                 39068_at 
                 “protein phosphatase 2, regulatory subunit B (B56), delta isoform” 
                 0.01 
               
               
                 192 
                 149_at 
                 “nuclear RNA helicase, DECD variant of DEAD box family” 
                 0.01 
               
               
                 193 
                 36597_at 
                 nucleolar and coiled-body phosphprotein 1 
                 0.01 
               
               
                 194 
                 37999_at 
                 “coproporphyrinogen oxidase (coproporphyria, harderoporphyria)” 
                 0.01 
               
               
                 195 
                 35114_at 
                 “nuclear receptor subfamily 1, group I, member 2” 
                 0.01 
               
               
                 196 
                 34767_at 
                 modulator of apoptosis 1 
                 0.01 
               
               
                 197 
                 1403_s_at 
                 small inducible cytokine A5 (RANTES) 
                 0.01 
               
               
                 198 
                 38899_s_at 
                 mitofusin 1 
                 0.01 
               
               
                 199 
                 41362_at 
                 “ATP-binding cassette, sub-family G (WHITE), member 1” 
                 0.01 
               
               
                 200 
                 33003_at 
                 NCK adaptor protein 2 
                 0.01 
               
               
                 201 
                 31687_f_at 
                 “hemoglobin, beta” 
                 0.01 
               
               
                 202 
                 38406_f_at 
                 “prostaglandin D2 synthase (21 kD, brain)” 
                 0.01 
               
               
                 203 
                 31623_f_at 
                 metallothionein 1A (functional) 
                 0.01 
               
               
                 204 
                 36996_at 
                 amplified in osteosarcoma 
                 0.01 
               
               
                 205 
                 895_at 
                 macrophage migration inhibitory factor (glycosylation-inhibiting factor) 
                 0.01 
               
               
                 206 
                 38095_i_at 
                 “major histocompatibility complex, class II, DP beta 1” 
                 0.01 
               
               
                 207 
                 38558_at 
                 myelin associated glycoprotein 
                 0.01 
               
               
                 208 
                 31956_f_at 
                 “ribosomal protein, large, P1” 
                 0.01 
               
               
                 209 
                 40448_at 
                 zinc finger protein homologous to Zfp-36 in mouse 
                 0.01 
               
               
                 210 
                 39120_at 
                 metallothionein 1L 
                 0.01 
               
               
                 211 
                 38350_f_at 
                 “tubulin, alpha 2” 
                 0.01 
               
               
                 212 
                 1424_s_at 
                 “D78577/FEATURE = expanded_cds/DEFINITION = D78576S2 Human DNA for 14-3-3 
                 0.01 
               
               
                   
                   
                 protein eta chain, exon2 and complete cds” 
               
               
                 213 
                 36681_at 
                 apolipoprotein D 
                 0.01 
               
               
                 214 
                 40886_at 
                 “Cluster Incl. L41498:  Homo sapiens  longation factor 1-alpha 1 (PTI-1) mRNA, complete cds/ 
                 0.01 
               
               
                   
                   
                 cds = (620,1816)/gb = L41498/gi = 927066/ug = Hs.181165/len = 2106” 
               
               
                 215 
                 39331_at 
                 “tubulin, beta polypeptide” 
                 0.01 
               
               
                 216 
                 36984_f_at 
                 haptoglobin-related protein 
                 0.01 
               
               
                 217 
                 41288_at 
                 matrix GIa protein 
                 0.01 
               
               
                 218 
                 38637_at 
                 lysyl oxidase 
                 0.01 
               
               
                 219 
                 35278_at 
                 “Cluster Incl. AI541542: libtest16.A02.r  Homo sapiens  cDNA, 5 end/clone_end = 5/ 
                 0.01 
               
               
                   
                   
                 gb = AI541542/gi = 4458915/ug = Hs.539/len = 639” 
               
               
                 220 
                 33458_r_at 
                 “H2B histone family, member L” 
                 0.01 
               
               
                 221 
                 32818_at 
                 “hexabrachion (tenascin C, cytotactin)” 
                 0.01 
               
               
                 222 
                 39830_at 
                 ribosomal protein L27 
                 0.01 
               
               
                 223 
                 34885_at 
                 synaptogyrin 2 
                 0.01 
               
               
                 224 
                 36152_at 
                 GDP dissociation inhibitor 1 
                 0.01 
               
               
                 225 
                 41143_at 
                 “Cluster Incl. U12022: Human calmodulin (CALM1) gene/cds = (199,648)/gb = U12022/ 
                 0.01 
               
               
                   
                   
                 gi = 2182171/ug = Hs.177656/len = 1526” 
               
               
                 226 
                 40580_r_at 
                 parathymosin 
                 0.01 
               
               
                 227 
                 33322_i_at 
                 stratifin 
                 0.01 
               
               
                 228 
                 41753_at 
                 “actinin, alpha 4” 
                 0.01 
               
               
                 229 
                 38972_at 
                 Cluster Incl. AF052169:  Homo sapiens  clone 24775 mRNA sequence/cds = UNKNOWN/ 
                 0.01 
               
               
                   
                   
                 gb = AF052169/gi = 3360480/ug = Hs.109438/len = 1385 
               
               
                 230 
                 41164_at 
                 immunoglobulin heavy constant mu 
                 0.01 
               
               
                 231 
                 35367_at 
                 “lectin, galactoside-binding, soluble, 3 (galectin 3)” 
                 0.01 
               
               
                 232 
                 32612_at 
                 “gelsolin (amyloidosis, Finnish type)” 
                 0.01 
               
               
                 233 
                 40096_at 
                 “ATP synthase, H+ transporting, mitochondrial F1 complex, alpha subunit, isoform 1, cardiac 
                 0.01 
               
               
                   
                   
                 muscle” 
               
               
                 234 
                 1916_s_at 
                 v-fos FBJ murine osteosarcoma viral oncogene homolog 
                 0.01 
               
               
                 235 
                 38379_at 
                 glycoprotein (transmembrane) nmb 
                 0.01 
               
               
                 236 
                 36736_f_at 
                 phosphoserine phosphatase 
                 0.01 
               
               
                 237 
                 40475_at 
                 calpain 6 
                 0.01 
               
               
                 238 
                 35837_at 
                 scrapie responsive protein 1 
                 0.01 
               
               
                 239 
                 34819_at 
                 “CD164 antigen, sialomucin” 
                 0.01 
               
               
                 240 
                 39072_at 
                 MAX-interacting protein 1 
                 0.01 
               
               
                 241 
                 35965_at 
                 heat shock 70 kD protein 6 (HSP70B‘) 
                 0.01 
               
               
                 242 
                 726_f_at 
                 growth hormone 1 
                 0.01 
               
               
                 243 
                 32786_at 
                 jun B proto-oncogene 
                 0.01 
               
               
                 244 
                 39741_at 
                 “hydroxyacyl-Coenzyme A dehydrogenase/3-ketoacyl-Coenzyme A thiolase/enoyl-Coenzyme A 
               
               
                   
                   
                 hydratase (trifunctional protein), beta subunit” 
                 0.01 
               
               
                 245 
                 38750_at 
                 Notch ( Drosophila ) homolog 3 
                 0.01 
               
               
                 246 
                 654_at 
                 MAX-interacting protein 1 
                 0.01 
               
               
                 247 
                 35310_at 
                 Cluster Incl. D45288: HUMHG2121  Homo sapiens  cDNA/gb = D45288/gi = 1136684/ 
                 0.01 
               
               
                   
                   
                 ug = Hs.57079/len = 1479 
               
               
                 248 
                 32218_at 
                 Cluster Incl. AF034176: AF034176  Homo sapiens  cDNA/clone = ntcon5-contig/gb = AF034176/ 
                 0.01 
               
               
                   
                   
                 gi = 2707738/ug = Hs.188882/len = 7232 
               
               
                 249 
                 836_at 
                 patched ( Drosophila ) homolog 
                 0.01 
               
               
                 250 
                 36181_at 
                 LIM and SH3 protein 1 
                 0.01 
               
               
                 251 
                 38738_at 
                 “SMT3 (suppressor of mif two 3, yeast) homolog 1” 
                 0.01 
               
               
                 252 
                 41634_at 
                 KIAA0256 gene product 
                 0.01 
               
               
                 253 
                 39046_at 
                 histone H2A.F/Z variant 
                 0.01 
               
               
                 254 
                 31740_s_at 
                 paired box gene 4 
                 0.01 
               
               
                 255 
                 40369_f_at 
                 “Cluster Incl. AL022723: dJ377H14.1 (major histocompatibility complex, class I, G (HLA 6.0))/ 
                 0.01 
               
               
                   
                   
                 cds = (120,1127)/gb = AL022723/gi = 5002624/ug = Hs.73885/len = 1508” 
               
               
                 256 
                 35298_at 
                 “eukaryotic translation initiation factor 3, subunit 7 (zeta, 66/67 kD)” 
                 0.01 
               
               
                 257 
                 605_at 
                 membrane protein of cholinergic synaptic vesicles 
                 0.01 
               
               
                 258 
                 39704_s_at 
                 high-mobility group (nonhistone chromosomal) protein isoforms I and Y 
                 0.01 
               
               
                 259 
                 117_at 
                 heat shock 70 kD protein 6 (HSP70B‘) 
                 0.01 
               
               
                 260 
                 31873_at 
                 renin-binding protein 
                 0.01 
               
               
                 261 
                 38791_at 
                 dolichyl-diphosphooligosaccharide-protein glycosyltransferase 
                 0.01 
               
               
                 262 
                 37769_at 
                 “endothelial differentiation, lysophosphatidic acid G-protein-coupled receptor, 4” 
                 0.01 
               
               
                 263 
                 39020_at 
                 CD27-binding (Siva) protein 
                 0.01 
               
               
                 264 
                 38378_at 
                 CD53 antigen 
                 0.01 
               
               
                 265 
                 40189_at 
                 SET translocation (myeloid leukemia-associated) 
                 0.01 
               
               
                 266 
                 40437_at 
                 DKFZP564G2022 protein 
                 0.01 
               
               
                 267 
                 38028_at 
                 neuronal specific transcription factor DAT1 
                 0.01 
               
               
                 268 
                 36791_g_at 
                 tropomyosin 1 (alpha) 
                 0.01 
               
               
                 269 
                 37034_at 
                 putative human HLA class II associated protein I 
                 0.01 
               
               
                 270 
                 35836_at 
                 nuclear distribution gene C ( A. nidulans ) homolog 
                 0.01 
               
               
                 271 
                 41177_at 
                 hypothetical protein FLJ12443 
                 0.01 
               
               
                 272 
                 35292_at 
                 HLA-B associated transcript 1 
                 0.01 
               
               
                 273 
                 1735_g_at 
                 “M60556/FEATURE = mRNA#1/DEFINITION = HUMTGFB3B Human transforming growth 
                 0.01 
               
               
                   
                   
                 factor beta-3 gene, 5 end” 
               
               
                 274 
                 1100_at 
                 interleukin-1 receptor-associated kinase 1 
                 0.01 
               
               
                 275 
                 255_s_at 
                 “inhibin, alpha” 
                 0.01 
               
               
                 276 
                 37967_at 
                 lymphocyte antigen 117 
                 0.01 
               
               
                 277 
                 38855_s_at 
                 neuroblastoma (nerve tissue) protein 
                 0.01 
               
               
                 278 
                 40834_at 
                 KIAA0300 protein 
                 0.01 
               
               
                 279 
                 33332_at 
                 CGI-96 protein 
                 0.01 
               
               
                 280 
                 32815_at 
                 “Cluster Incl. AI687419: tp95h03.x1  Homo sapiens  cDNA, 3 end/clone = IMAGE-2207093/ 
                 0.01 
               
               
                   
                   
                 clone_end = 3/gb = AI687419/gi = 4898713/ug = Hs.203410/len = 286” 
               
               
                 281 
                 35780_at 
                 KIAA0657 protein 
                 0.01 
               
               
                 282 
                 36453_at 
                 KIAA0711 gene product 
                 0.01 
               
               
                 283 
                 37346_at 
                 ADP-ribosylation factor 5 
                 0.01 
               
               
                 284 
                 31440_at 
                 “transcription factor 7 (T-cell specific, HMG-box)” 
                 0.01 
               
               
                 285 
                 36669_at 
                 FBJ murine osteosarcoma viral oncogene homolog B 
                 0.01 
               
               
                 286 
                 35309_at 
                 “suppression of tumorigenicity 14 (colon carcinoma, matriptase, epithin)” 
                 0.01 
               
               
                 287 
                 34789_at 
                 “serine (or cysteine) proteinase inhibitor, clade B (ovalbumin), member 6” 
                 0.01 
               
               
                 288 
                 555_at 
                 GTP-binding protein homologous to  Saccharomyces cerevisiae  SEC4 
                 0.01 
               
               
                 289 
                 36711_at 
                 chromosome 22 open reading frame 5 
                 0.01 
               
               
                 290 
                 171_at 
                 von Hippel-Lindau binding protein 1 
                 0.01 
               
               
                 291 
                 41000_at 
                 checkpoint suppressor 1 
                 0.01 
               
               
                 292 
                 39339_at 
                 KIAA0792 gene product 
                 0.01 
               
               
                 293 
                 40082_at 
                 “fatty-acid-Coenzyme A ligase, long-chain 2” 
                 0.01 
               
               
                 294 
                 36267_at 
                 nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-like 1 
                 0.01 
               
               
                 295 
                 33683_at 
                 Cluster Incl. D50525: Human mRNA for TI-227H/cds = UNKNOWN/gb = D50525/gi = 1167502/ 
                 0.01 
               
               
                   
                   
                 ug = Hs.184914/len = 3911 
               
               
                 296 
                 40044_at 
                 ELL gene (11-19 lysine-rich leukemia gene) 
                 0.01 
               
               
                 297 
                 34060_g_at 
                 “pvt-1 (murine) oncogene homolog, MYC activator” 
                 0.01 
               
               
                 298 
                 33282_at 
                 ladinin 1 
                 0.01 
               
               
                 299 
                 37279_at 
                 GTP-binding protein overexpressed in skeletal muscle 
                 0.01 
               
               
                 300 
                 38031_at 
                 KIAA0111 gene product 
                 0.01 
               
               
                 301 
                 38011_at 
                 RPB5-mediating protein 
                 0.01 
               
               
                 302 
                 40910_at 
                 “capping protein (actin filament) muscle Z-line, alpha 1” 
                 0.01 
               
               
                 303 
                 1801_at 
                 BRCA1 associated RING domain 1 
                 0.01 
               
               
                 304 
                 41774_at 
                 ADP-ribosylation factor 4-like 
                 0.01 
               
               
                 305 
                 641_at 
                 presenilin 1 (Alzheimer disease 3) 
                 0.01 
               
               
                 306 
                 39828_at 
                 ADP-ribosylation factor-like 7 
                 0.01 
               
               
                 307 
                 37147_at 
                 stem cell growth factor; lymphocyte secreted C-type lectin 
                 0.01 
               
               
                 308 
                 36827_at 
                 golgi phosphoprotein 1 
                 0.01 
               
               
                 309 
                 932_i_at 
                 “zinc finger protein 91 (HPF7, HTF10)” 
                 0.01 
               
               
                 310 
                 1944_f_at 
                 “AF001359/FEATURE=/DEFINITION = AF001359  Homo sapiens  DNA mismatch repair 
                 0.01 
               
               
                   
                   
                 protein (hMLH1) mRNA, alternatively spliced, partial cds” 
               
               
                 311 
                 36208_at 
                 bromodomain-containing 2 
                 0.01 
               
               
                 312 
                 37217_at 
                 “hemoglobin, zeta” 
                 0.01 
               
               
                 313 
                 39064_at 
                 “5,10-methenyltetrahydrofolate synthetase (5-formyltetrahydrofolate cyclo-ligase)” 
                 0.01 
               
               
                 314 
                 32510_at 
                 “aldo-keto reductase family 7, member A2 (aflatoxin aldehyde reductase)” 
                 0.01 
               
               
                 315 
                 1062_g_at 
                 “interleukin 10 receptor, alpha” 
                 0.01 
               
               
                 316 
                 37679_at 
                 interferon-related developmental regulator 1 
                 0.01 
               
               
                 317 
                 34080_at 
                 N-acetylated alpha-linked acidic dipeptidase-like; ILEAL DIPEPTIDYLPEPTIDASE 
                 0.01 
               
               
                 318 
                 1477_s_at 
                 “cytochrome P450, subfamily IIC (mephenytoin 4-hydroxylase), polypeptide 18” 
                 0.01 
               
               
                 319 
                 1389_at 
                 “membrane metallo-endopeptidase (neutral endopeptidase, enkephalinase, CALLA, CD10)” 
                 0.01 
               
               
                 320 
                 35781_g_at 
                 KIAA0657 protein 
                 0.01 
               
               
                 321 
                 36987_at 
                 lamin B2 
                 0.01 
               
               
                 322 
                 36946_at 
                 dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A 
                 0.01 
               
               
                 323 
                 36150_at 
                 KIAA0842 protein 
                 0.01 
               
               
                 324 
                 40507_at 
                 “solute carrier family 2 (facilitated glucose transporter), member 1” 
                 0.01 
               
               
                 325 
                 34079_at 
                 inactivation escape 1 
                 0.01 
               
               
                 326 
                 34808_at 
                 KIAA0999 protein 
                 0.01 
               
               
                 327 
                 37873_g_at 
                 jerky (mouse) homolog 
                 0.01 
               
               
                 328 
                 34799_at 
                 hypothetical protein 24636 
                 0.01 
               
               
                 329 
                 35615_at 
                 block of proliferation 1 
                 0.01 
               
               
                 330 
                 34442_at 
                 Cluster Incl. U72943: U72943  Homo sapiens  cDNA/gb = U72943/gi = 5763294/ug = Hs.106642/ 
                 0.01 
               
               
                   
                   
                 len = 1667 
               
               
                 331 
                 32433_at 
                 ribosomal protein L15 
                 0.01 
               
               
                 332 
                 40503_at 
                 “myosin-binding protein C, slow-type” 
                 0.01 
               
               
                 333 
                 40014_at 
                 semaphorin Y 
                 0.01 
               
               
                 334 
                 38633_at 
                 metastasis associated 1 
                 0.01 
               
               
                 335 
                 36807_at 
                 TED protein 
                 0.01 
               
               
                 336 
                 40227_at 
                 “Cluster Incl. D29810: Human mRNA for unknown product, partial cds/cds = (0.1096)/ 
                 0.01 
               
               
                   
                   
                 gb = D29810/gi = 704440/ug = Hs.153445/len = 1388” 
               
               
                 337 
                 32841_at 
                 zinc finger protein 9 (a cellular retroviral nucleic acid binding protein) 
                 0.01 
               
               
                 338 
                 1850_at 
                 “mutL ( E. coli ) homolog 1 (colon cancer, nonpolyposis type 2)” 
                 0.01 
               
               
                 339 
                 35956_s_at 
                 pregnancy specific beta-1-glycoprotein 7 
                 0.01 
               
               
                 340 
                 34287_at 
                 chromosome 21 open reading frame 80 
                 0.01 
               
               
                 341 
                 35999_r_at 
                 KIAA0781 protein 
                 0.01 
               
               
                 342 
                 1230_g_at 
                 cisplatin resistance associated 
                 0.01 
               
               
                 343 
                 31388_at 
                 early lymphoid activation protein 
                 0.01 
               
               
                 344 
                 41034_s_at 
                 “sulfotransferase family, cytosolic, 2B, member 1” 
                 0.01 
               
               
                 345 
                 32037_r_at 
                 ribonuclease P (14 kD) 
                 0.01 
               
               
                 346 
                 32773_at 
                 “major histocompatibility complex, class II, DQ alpha 1” 
                 0.01 
               
               
                 347 
                 33263_at 
                 Cluster Incl. X67098:  H. sapiens  rTS alpha mRNA containing four open reading frames/ 
                 0.01 
               
               
                   
                   
                 cds = UNKNOWN/gb = X67098/gi = 475908/ug = Hs.180433/len = 1817 
               
               
                 348 
                 40143_at 
                 KIAA0140 gene product 
                 0.01 
               
               
                 349 
                 37509_at 
                 cytokine receptor-like molecule 9 
                 0.01 
               
               
                 350 
                 39164_at 
                 ariadne ( Drosophila ) homolog 2 
                 0.01 
               
               
                 351 
                 39863_at 
                 KIAA0296 gene product 
                 0.01 
               
               
                 352 
                 36214_at 
                 Kruppel-like factor 4 (gut) 
                 0.01 
               
               
                 353 
                 36466_at 
                 “dystrobrevin, alpha” 
                 0.01 
               
               
                 354 
                 38319_at 
                 “CD3D antigen, delta polypeptide (TiT3 complex)” 
                 0.01 
               
               
                 355 
                 38675_at 
                 small nuclear ribonucleoprotein polypeptide C 
                 0.01 
               
               
                 356 
                 39112_at 
                 “upstream transcription factor 2, c-fos interacting” 
                 0.01 
               
               
                 357 
                 38968_at 
                 SH3-domain binding protein 5 (BTK-associated) 
                 0.01 
               
               
                 358 
                 34306_at 
                 muscleblind ( Drosophila )-like 
                 0.01 
               
               
                 359 
                 37868_s_at 
                 myelin oligodendrocyte glycoprotein 
                 0.01 
               
               
                 360 
                 36457_at 
                 guanine monphosphate synthetase 
                 0.01 
               
               
                 361 
                 41514_s_at 
                 mitochondrial ribosomal protein L9 
                 0.01 
               
               
                 362 
                 36313_at 
                 “Cluster Incl. M55267: Human EV12 protein gene/cds = (0.698)/gb = M55267/gi = 182279/ 
                 0.01 
               
               
                   
                   
                 ug = Hs.41846/len = 699” 
               
               
                 363 
                 1055_g_at 
                 replication factor C (activator 1) 4 (37 kD) 
                 0.01 
               
               
                 364 
                 34629_at 
                 p53-induced protein 
                 0.01 
               
               
                 365 
                 41565_at 
                 ataxin 2 related protein 
                 0.01 
               
               
                 366 
                 36740_at 
                 “double C2-like domains, alpha” 
                 0.01 
               
               
                 367 
                 36580_at 
                 hypothetical protein FLJ13910 
                 0.01 
               
               
                 368 
                 1680_at 
                 growth factor receptor-bound protein 7 
                 0.01 
               
               
                 369 
                 35238_at 
                 TNF receptor-associated factor 5 
                 0.01 
               
               
                 370 
                 733_at 
                 Mucin 
                 0.01 
               
               
                 371 
                 38449_at 
                 hypthetical protein PRO2389 
                 0.01 
               
               
                 372 
                 41547_at 
                 “BUB3 (budding uninhibited by benzimidazoles 3, yeast) homolog” 
                 0.01 
               
               
                 373 
                 31778_at 
                 “gap junction protein, alpha 8, 50 kD (connexin 50)” 
                 0.01 
               
               
                 374 
                 39255_at 
                 protein C (inactivator of coagulation factors Va and VIIIa) 
                 0.01 
               
               
                 375 
                 33921_at 
                 “glucose-6-phosphatase, transport (glucose-6-phosphate) protein 1” 
                 0.01 
               
               
                 376 
                 41174_at 
                 RAN binding protein 2-like 1 
                 0.01 
               
               
                 377 
                 33147_at 
                 likely ortholog of mouse zinc finger protein Zfr 
                 0.01 
               
               
                 378 
                 843_at 
                 “protein tyrosine phosphatase type IVA, member 1” 
                 0.01 
               
               
                 379 
                 34069_s_at 
                 “Cluster Incl. S79325: SYT . . . SSX1 {translocation breakpoint} [human, synovial sarcomas, 
                 0.01 
               
               
                   
                   
                 mRNA Partial Mutant, 3 genes, 585 nt]/cds = (240,476)/gb = S79325/gi = 1087047/ 
               
               
                   
                   
                 ug = Hs.194759/len = 585” 
               
               
                 380 
                 35317_at 
                 meningioma expressed antigen 5 (hyaluronidase) 
                 0.01 
               
               
                 381 
                 40155_at 
                 actin binding LIM protein 1 
                 0.01 
               
               
                 382 
                 35763_at 
                 KIAA0540 protein 
                 0.01 
               
               
                 383 
                 41107_at 
                 syntaphilin 
                 0.01 
               
               
                 384 
                 32894_at 
                 leucine-rich neuronal protein 
                 0.01 
               
               
                 385 
                 40788_at 
                 adenylate kinase 2 
                 0.01 
               
               
                 386 
                 34009_at 
                 cancer/testis antigen 2 
                 0.01 
               
               
                 387 
                 36079_at 
                 quinone oxidoreductase homolog 
                 0.01 
               
               
                 388 
                 41114_at 
                 KIAA0807 protein 
                 0.01 
               
               
                 389 
                 31731_at 
                 chromobox homolog 4 ( Drosophila  Pc class) 
                 0.01 
               
               
                 390 
                 32897_at 
                 “5,10-methylenetetrahydrofolate reductase (NADPH)” 
                 0.01 
               
               
                 391 
                 34949_at 
                 KIAA1048 protein 
                 0.01 
               
               
                 392 
                 37506_at 
                 Huntingtin-interacting protein A 
                 0.01 
               
               
                 393 
                 37791_at 
                 “Cluster Incl. N29966: yw53g02.s1  Homo sapiens  cDNA, 3 end/clone = IMAGE-255986/ 
                 0.01 
               
               
                   
                   
                 clone_end = 3/gb = N29966/gi = 1148486/ug = Hs.125231/len = 496” 
               
               
                 394 
                 36964_at 
                 “membrane-bound transcription factor protease, site 1” 
                 0.01 
               
               
                 395 
                 39585_at 
                 cell cycle related kinase 
                 0.01 
               
               
                 396 
                 34845_at 
                 CGI-51 protein 
                 0.01 
               
               
                 397 
                 34953_i_at 
                 “phosphodiesterase 5A, cGMP-specific” 
                 0.01 
               
               
                 398 
                 32246_g_at 
                 putative methyltransferase 
                 0.01 
               
               
                 399 
                 38361_g_at 
                 RAS guanyl releasing protein 2 (calcium and DAG-regulated) 
                 0.01 
               
               
                 400 
                 31794_at 
                 “5′-nucleotidase (purine), cytosolic type B” 
                 0.01 
               
               
                 401 
                 40576_f_at 
                 heterogeneous nuclear ribonucleoprotein D-like 
                 0.01 
               
               
                 402 
                 31579_at 
                 “Cluster Incl. AF005082:  Homo sapiens  skin-specific protein (xp33) mRNA, partial cds/ 
                 0.01 
               
               
                   
                   
                 cds = (0.287)/gb = AF005082/gi = 2589191/ug = Hs.113261/len = 303” 
               
               
                 403 
                 31314_at 
                 bone morphogenetic protein 3 (osteogenic) 
                 0.01 
               
               
                 404 
                 40197_at 
                 HYA22 protein 
                 0.01 
               
               
                 405 
                 38394_at 
                 KIAA0089 protein 
                 0.01 
               
               
                 406 
                 36770_at 
                 “signal transducer and activator of transcription 2, 113 kD” 
                 0.01 
               
               
                 407 
                 39976_at 
                 KIAA1785 protein 
                 0.01 
               
               
                 408 
                 1281_f_at 
                 Serine/Threonine Kinase 
                 0.01 
               
               
                 409 
                 36553_at 
                 acetylserotonin O-methyltransferase-like 
                 0.01 
               
               
                 410 
                 31892_at 
                 “protein tyrosine phosphatase, receptor type, M” 
                 0.01 
               
               
                 411 
                 32067_at 
                 cAMP responsive element modulator 
                 0.01 
               
               
                 412 
                 35727_at 
                 hypothetical protein FLJ20517 
                 0.01 
               
               
                 413 
                 35524_at 
                 “complement component 8, gamma polypeptide” 
                 0.01 
               
               
                 414 
                 33392_at 
                 DKFZP434J154 protein 
                 0.01 
               
               
                 415 
                 36531_r_at 
                 hypothetical protein 
                 0.01 
               
               
                 416 
                 32978_g_at 
                 chromosome 6 open reading frame 32 
                 0.01 
               
               
                 417 
                 37907_at 
                 coagulation factor VIII-associated (intronic transcript) 
                 0.01 
               
               
                 418 
                 34585_at 
                 distal-less homeo box 2 
                 0.01 
               
               
                 419 
                 32845_at 
                 heparan sulfate proteoglycan 2 (perlecan) 
                 0.01 
               
               
                 420 
                 37966_at 
                 “parvin, beta” 
                 0.01 
               
               
                 421 
                 37188_at 
                 phosphoenolpyruvate carboxykinase 2 (mitochondrial) 
                 0.01 
               
               
                 422 
                 478_g_at 
                 interferon regulatory factor 5 
                 0.01 
               
               
                 423 
                 32647_at 
                 vesicle-associated soluble NSF attachment protein receptor (v-SNARE; homolog of  S.   
                 0.01 
               
               
                   
                   
                   cerevisiae  VTI1) 
               
               
                 424 
                 35540_at 
                 hyaluronoglucosaminidase 3 
                 0.01 
               
               
                 425 
                 37601_at 
                 “solute carrier family 22 (extraneuronal monoamine transporter), member 3” 
                 0.01 
               
               
                 426 
                 32124_at 
                 hypothetical protein LOC57187 
                 0.01 
               
               
                 427 
                 36642_at 
                 “Cluster Incl. J00287: Human pepsinogen gene/cds = (55,1221)/gb = J00287/gi = 189798/ 
                 0.01 
               
               
                   
                   
                 ug = Hs.75558/len = 1381” 
               
               
                 428 
                 35989_at 
                 calcineurin-binding protein calsarcin-1 
                 0.01 
               
               
                 429 
                 349_g_at 
                 kinesin-like 2 
                 0.01 
               
               
                 430 
                 33173_g_at 
                 hypothetical protein FLJ10849 
                 0.01 
               
               
                 431 
                 31539_r_at 
                 “Cluster Incl. L23852:  Homo sapiens  (clone Z146) retinal mRNA, 3 end and repeat region/ 
                 0.01 
               
               
                   
                   
                 cds = (0.241)/gb = L23852/gi = 393126/ug = Hs.73838/len = 1711” 
               
               
                 432 
                 34816_at 
                 trinucleotide repeat containing 12 
                 0.01 
               
               
                 433 
                 32856_at 
                 KIAA0819 protein 
                 0.01 
               
               
                 434 
                 31662_at 
                 vacuolar protein sorting 45A (yeast homolog) 
                 0.01 
               
               
                 435 
                 40516_at 
                 aryl hydrocarbon receptor 
                 0.01 
               
               
                 436 
                 35622_at 
                 neuronal Shc adaptor homolog 
                 0.01 
               
               
                 437 
                 36653_g_at 
                 uroporphyrinogen III synthase (congenital erythropoietic porphyria) 
                 0.01 
               
               
                 438 
                 1150_at 
                 “protein tyrosine phosphatase, receptor type, E” 
                 0.01 
               
               
                 439 
                 1229_at 
                 cisplatin resistance associated 
                 0.01 
               
               
                 440 
                 36625_at 
                 peroxisomal long-chain acyl-coA thioesterase 
                 0.01 
               
               
                 441 
                 40572_at 
                 “Cluster Incl. N51314: yz15b04.s1  Homo sapiens  cDNA, 3 end/clone = IMAGE-283087/ 
                 0.01 
               
               
                   
                   
                 clone_end = 3/gb = N51314/gi = 1192480/ug = Hs.170241/len = 472” 
               
               
                 442 
                 31897_at 
                 downregulated in ovarian cancer 1 
                 0.01 
               
               
                 443 
                 558_at 
                 keratin 1 (epidermolytic hyperkeratosis) 
                 0.01 
               
               
                 444 
                 39751_at 
                 DHHC1 protein 
                 0.01 
               
               
                 445 
                 40892_s_at 
                 DNA segment on chromosome X (unique) 9879 expressed sequence 
                 0.01 
               
               
                 446 
                 526_s_at 
                 postmeiotic segregation increased ( S. cerevisiae ) 2 
                 0.01 
               
               
                 447 
                 359_at 
                 “interleukin 13 receptor, alpha 1” 
                 0.01 
               
               
                 448 
                 36456_at 
                 DKFZP564I052 protein 
                 0.01 
               
               
                 449 
                 39298_at 
                 “alpha2,3-sialyltransferase” 
                 0.01 
               
               
                 450 
                 1495_at 
                 latent transforming growth factor beta binding protein 1 
                 0.01 
               
               
                 451 
                 31649_at 
                 HGC6.1.1 protein 
                 0.01 
               
               
                 452 
                 41722_at 
                 nicotinamide nucleotide transhydrogenase 
                 0.01 
               
               
                 453 
                 38204_at 
                 KIAA0406 gene product 
                 0.01 
               
               
                 454 
                 1885_at 
                 “excision repair cross-complementing rodent repair deficiency, complementation group 3 
                 0.01 
               
               
                   
                   
                 (xeroderma pigmentosum group B complementing)” 
               
               
                 455 
                 36005_at 
                 suppressor of white apricot homolog 2 
                 0.01 
               
               
                 456 
                 37180_at 
                 “phospholipase C, gamma 2 (phosphatidylinositol-specific)” 
                 0.01 
               
               
                 457 
                 33354_at 
                 E3 ubiquitin ligase SMURF2 
                 0.01 
               
               
                 458 
                 32624_at 
                 DKFZP566D133 protein 
                 0.01 
               
               
                 459 
                 32132_at 
                 KIAA0675 gene product 
                 0.01 
               
               
                 460 
                 33411_g_at 
                 “integrin, alpha 6” 
                 0.01 
               
               
                 461 
                 34675_at 
                 Cluster Incl. AL080210:  Homo sapiens  mRNA; cDNA DKFZp586G0623 (from clone 
                 0.01 
               
               
                   
                   
                 DKFZp586G0623)/cds = UNKNOWN/gb = AL080210/gi = 5262699/ug = Hs.23437/len = 1388 
               
               
                 462 
                 37710_at 
                 “MADS box transcription enhancer factor 2, polypeptide C (myocyte enhancer factor 2C)” 
                 0.01 
               
               
                 463 
                 794_at 
                 “protein tyrosine phosphatase, non-receptor type 6” 
                 0.01 
               
               
                 464 
                 39016_r_at 
                 keratin 6A 
                 0.01 
               
               
                 465 
                 1909_at 
                 B-cell CLL/lymphoma 2 
                 0.01 
               
               
                 466 
                 36564_at 
                 Cluster Incl. W27419: 31a10  Homo sapiens  cDNA/gb = W27419/gi = 1307241/ug = Hs.64239/ 
                 0.01 
               
               
                   
                   
                 len = 803 
               
               
                 467 
                 622_at 
                 “RAB6A, member RAS oncogene family” 
                 0.01 
               
               
                 468 
                 40201_at 
                 dopa decarboxylase (aromatic L-amino acid decarboxylase) 
                 0.01 
               
               
                 469 
                 31894_at 
                 centromere protein C 1 
                 0.01 
               
               
                 470 
                 41100_at 
                 tumor up-regulated CARD-containing antagonist of caspase nine 
                 0.01 
               
               
                 471 
                 33202_f_at 
                 Friedreich ataxia 
                 0.01 
               
               
                 472 
                 394_at 
                 bleomycin hydrolase 
                 0.01 
               
               
                 473 
                 31485_at 
                 “Cluster Incl. M57423:  Homo sapiens  phosphoribosylpyrophosphate synthetase subunit III 
                 0.01 
               
               
                   
                   
                 mRNA, 3 end/cds = (81,1037)/gb = M57423/gi = 190521/ug = Hs.169284/len = 1091” 
               
               
                 474 
                 32962_at 
                 cystathionase (cystathionine gamma-lyase) 
                 0.01 
               
               
                 475 
                 39480_s_at 
                 KIAA1454 protein 
                 0.01 
               
               
                 476 
                 362_at 
                 “protein kinase C, zeta” 
                 0.01 
               
               
                 477 
                 33270_i_at 
                 Dmx-like 1 
                 0.01 
               
               
                 478 
                 40086_at 
                 KIAA0261 protein 
                 0.01 
               
               
                 479 
                 966_at 
                 RAD54 ( S.cerevisiae )-like 
                 0.01 
               
               
                 480 
                 1108_s_at 
                 EphA1 
                 0.01 
               
               
                 481 
                 962_at 
                 BMX non-receptor tyrosine kinase 
                 0.01 
               
               
                 482 
                 1610_s_at 
                 “J00139/FEATURE = cds/DEFINITION = HUMFOL5 Human dihydrofolate reductase gene, 
                 0.01 
               
               
                   
                   
                 exon 6 and 3 flank” 
               
               
                 483 
                 35650_at 
                 KIAA0356 gene product 
                 0.01 
               
               
                 484 
                 35025_at 
                 “small inducible cytokine subfamily B (Cys-X-Cys), member 5 (epithelial-derived neutrophil- 
                 0.01 
               
               
                   
                   
                 activating peptide 78)” 
               
               
                 485 
                 1529_at 
                 hypothetical protein CG003 
                 0.01 
               
               
                 486 
                 177_at 
                 “phospholipase D1, phophatidylcholine-specific” 
                 0.01 
               
               
                 487 
                 496_s_at 
                 “interleukin 11 receptor, alpha” 
                 0.01 
               
               
                 488 
                 33998_at 
                 neurotensin 
                 0.01 
               
               
                 489 
                 1384_at 
                 “M64930/FEATURE=/DEFINITION = HUMPROP2AB Human protein phosphatase 2A 
                 0.01 
               
               
                   
                   
                 beta subunit mRNA, complete cds” 
               
               
                 490 
                 36898_r_at 
                 “primase, polypeptide 2A (58 kD)” 
                 0.01