Patent Publication Number: US-2012046186-A1

Title: Gene Expression Markers for Prediction of Response to Platinum-Based Chemotherapy Drugs

Description:
This application claims priority under 35 U.S.C. §119(e) to U.S. Provisional Application No. 61/375,782, filed on Aug. 20, 2010, which is hereby incorporated by reference in its entirety. 
    
    
     FIELD OF THE INVENTION 
     The present invention relates to genes, the expression levels of which are useful for predicting response of cancer cells and cancer patients to a platinum-based chemotherapy drug. 
     BACKGROUND 
     Platinum-based cancer chemotherapies have had a major clinical impact in the treatment of patients with cancer. Furthermore, an emerging clinical strategy is that the optimal efficacy of novel targeted therapies may be in combination with existing cytotoxic DNA-damaging agents, including oxaliplatin. Given the expanding role of oxaliplatin in cancer treatment, it has become increasingly important to understand molecular predictors of oxaliplatin response in order to provide for more personalized administration of chemotherapy. 
     Oxaliplatin is a third-generation platinum-based chemotherapeutic agent that has significant activity in colorectal cancer (CRC). Adjuvant therapy with oxaliplatin, combined with fluoropyrimidine-based chemotherapy, results in significant increases in disease-free survival rates in patients with stage II/III colon cancer (Andre, T., et al., “Oxaliplatin, Fluorouracil, and Leucovorin as Adjuvant Treatment for Colon Cancer,”  N. Engl. J. Med.,  2004. 350(23): p. 2343-51). In the metastatic setting, combination therapy with 5-FU and oxaliplatin is the most commonly used front-line regimen, with superior response rates and longer survival than 5-FU alone (Rothenberg, M. L., et al., “Superiority of Oxaliplatin and Fluorouracil-Leucovorin Compared with Either Therapy Alone in Patients with Progressive Colorectal Cancer After Irinotecan and Fluorouracil-Leucovorin: Interim Results of a Phase III Trial,”  J. Clin. Oncol.,  2003. 21(11): p. 2059-69; de Gramont, A., et al., “Reintroduction of Oxaliplatin is Associated With Improved Survival in Advanced Colorectal Cancer,”  J. Clin. Oncol.,  2007. 25(22): p. 3224-9). However, it is apparent that not all patients benefit from oxaliplatin treatment, and in the face of significant side-effects associated with oxaliplatin, most notably prolonged neurotoxicity, there is a need for clinical tools to guide use of oxaliplatin in those patients who are most likely to derive benefit. 
     Oxaliplatin induces cytotoxicity through the formation of platinum-DNA adducts, which in turn, activate multiple signaling pathway (Kelland, L., “The Resurgence of Platinum-Based Cancer Chemotherapy,”  Nat. Rev. Cancer,  2007. 7(8): p. 573-84). Alterations in drug efflux and uptake, DNA repair and inactivation of the apoptosis pathways have been hypothesized to promote resistance to platinum agents such as carboplatin and cisplatin (Wang, D. and S. J. Lippard, “Cellular Processing of Platinum Anticancer Drugs,”  Nat. Rev. Drug Discov.,  2005. 4(4): p. 307-320; Siddick, Z. H., “Cisplatin: Mode of Cytotoxic Action and Molecular Basis of Resistance,”  Oncogene,  2003. 22(47): p. 7265-79). None of these putative markers of oxaliplatin sensitivity and resistance have been clinically validated, and at present, there are no markers established in clinical use for selecting CRC patients for oxaliplatin therapy. 
     The current clinical practice used for making CRC treatment decisions is determined by clinical and pathological staging. However, these prognostic tools do not predict drug response in an individual patient. Recent insights into the genomics of cancers have enabled development of diagnostic tests that inform clinical decisions for cancer patients (Harris, L., et al., “American Society of Clinical Oncology 2007 Update of Recommendations for the Use of Tumor Markers in Breast Cancer,”  J. Clin. Oncol.,  2007. 25(33): p. 5287-312; Dunn., L. and A. Demichele, “Genomic Predictors of Outcome and Treatment Response in Breast Cancer,”  Mol. Diagn. Ther.,  2009. 13(2): p. 73-90; Paik, S., et al., “A Multigene Assay to Predict Recurrence of Tamoxifen-Treated, Node-Negative Breast Cancer,”  N. Engl. J. Med.,  2004. 351(27): p. 2817-25; Paik, S., et al., “Gene Expression and Benefit of Chemotherapy in Women With Node-Negative, Estrogen Receptor-Positive Breast Cancer,”  J. Clin. Oncol.,  2006. 24(23): p. 3726-34). To further advance the personalization of CRC treatment, there is a need for a greater understanding of the genetic alterations in CRC tumors that are associated with patient sensitivity or resistance to oxaliplatin. 
     SUMMARY 
     The present invention provides response indicator genes for platinum-based chemotherapy drugs. These genes are provided in Tables 1-4. The present invention also provides gene subsets of the response indicator genes based on their known function. These gene subsets include, but are not limited to, a drug resistance group, drug transporter group, apoptosis group, DNA damage repair group, cell cycle group, p53 pathway group, and nucleotide excision repair (NER) group. Table 1 provides a gene subset in which each gene may be grouped. The present invention also provides methods of identifying gene cliques, i.e. genes that co-express with a response indicator gene and exhibit correlation of expression with the response indicator gene, and thus may be substituted for that response indicator gene in an assay. 
     In an embodiment of the invention, increased expression level of one or more response indicator genes selected from ATP6V0C, BCL10, BCL2L10, BFAR, BRIP1, CARD6, CCND1, CDC20, CDC25A, CFLAR, CHAF1A, CRADD, CUL4B, DFFA, E2F2, E2F4, E2F6, GADD45B, HMG20B, IL8, LTBR, MBD2, MBD3, MBD4, MCM3, MCM4, MCM6, MGST3, MPG, MRPL3, MSH4, NHEJ1, OGT, PAICS, PPP2R5C, PRDX4, PTTG1, RAD51L1, RARA, RBM4, RECQL, RRM1, SHFM1, SPO11, TMEM30A, UBE2A, UBE2S, XAB2, and XRCC2 is negatively correlated with a likelihood of a positive response to a platinum-based chemotherapy drug. 
     In another embodiment of the invention, increased expression level of one or more response indicator genes selected from ABL1, APAF1, BAX, CARD4, CASP5, CCT5, CDKN1A, CDKN3, CIDEA, CRIP2, CUL1, CYP1A2, DNMT1, ERCC4, FANCE, GSTT1, GSTZ1, GTF2H5, KPNA2, MRPS12, MSH5, NFKB1, PTEN, SMARCA4, SND1, SOX4, SUMO1, TARS, TNFRSF10A, TNFSF8, TP53, XPC, and XRCC3 is positively correlated with a likelihood of a positive response to a platinum-based chemotherapy drug. 
     In a specific embodiment of the invention, increased expression level of one or more genes selected from BCL10, BCL2L10, BFAR, BRIP1, CHAF1A, CUL4B, DFFA, IL8, LTBR, MBD2, MBD4, MCM3, MCM4, MCM6, MPG, MSH4, NHEJ1, PRDX4, PTTG1, RAD51L1, RRM1, SHFM1, and TMEM30A is negatively correlated with a likelihood of a positive response to a platinum-based chemotherapy drug, and increased expression level of one or more genes selected from CDKN1A, KPNA2, SUMO1, and TP53 is positively correlated with a likelihood of a positive response to a platinum-based chemotherapy drug. 
     The present invention further provides methods and compositions for predicting the likelihood that a patient with cancer will exhibit a positive response to a treatment comprising a platinum-based chemotherapy drug based on the expression level of one or more response indicator genes in a tumor sample obtained from the patient. Specifically, the method comprises assaying or measuring an expression level of one or more response indicator gene products. The response indicator gene is selected from any one of the genes listed in Tables 1-4. In an embodiment of the invention, the response indicator gene is one or more selected from ABL1, APAF1, ATP6V0C, BAX, BCL10, BCL2L10, BFAR, BRIP1, CARD4, CARD6, CASP5, CCND1, CCT5, CDC20, CDC25A, CDKN1A, CDKN3, CFLAR, CHAF1A, CIDEA, CRADD, CRIP2, CUL1, CUL4B, CYP1A2, DFFA, DNMT1, E2F2, E2F4, E2F6, ERCC4, FANCE, GADD45B, GSTT1, GSTZ1, GTF2H5, HMG20B, IL8, KPNA2, LTBR, MBD2, MBD3, MBD4, MCM3, MCM4, MCM6, MGST3, MPG, MRPL3, MRPS12, MSH4, MSH5, NFKB1, NHEJ1, OGT, PAICS, PPP2R5c, PRDX4, PTEN, PTTG1, RAD51L1, RARA, RBM4, RECQL, RRM1, SHFM1, SMARCA4, SND1, SOX4, SPO11, SUMO1, TARS, TMEM30A, TNFRSF10A, TNFSF8, TP53, UBE2A, UBE2S, XAB2, XPC, XRCC2, and XRCC3. In another embodiment of the invention, the response indicator gene is one or more selected from BCL10, BCL2L10, BFAR, BRIP1, CDKN1A, CHAF1A, CUL4B, DFFA, IL8, KPNA2, LTBR, MBD2, MBD4, MCM3, MCM4, MCM6, MPG, MSH4, NHEJ1, PRDX4, PTTG1, RAD51L1, RRM1, SHFM1, SUMO1, TMEM30A, and TP53. In a further embodiment, the expression level of the response indicator gene is normalized. The expression level or the normalized expression level is used to predict the likelihood of a positive response, wherein increased expression level or increased normalized expression level of one or more response indicator genes selected from ATP6V0C, BCL10, BCL2L10, BFAR, BRIP1, CARD6, CCND1, CDC20, CDC25A, CFLAR, CHAF1A, CRADD, CUL4B, DFFA, E2F2, E2F4, E2F6, GADD45B, HMG20B, IL8, LTBR, MBD2, MBD3, MBD4, MCM3, MCM4, MCM6, MGST3, MPG, MRPL3, MSH4, NHEJ1, OGT, PAICS, PPP2R5c, PRDX4, PTTG1, RAD51L1, RARA, RBM4, RECQL, RRM1, SHFM1, SPO11, TMEM30A, UBE2A, UBE2S, XAB2, and XRCC2 is negatively correlated with a likelihood that the patient will exhibit a positive response to a treatment comprising a platinum-based chemotherapy drug, and increased expression level or increased normalized expression level of one or more response indicator genes selected from ABL1, APAF1, BAX, CARD4, CASP5, CCT5, CDKN1A, CDKN3, CIDEA, CRIP2, CUL1, CYP1A2, DNMT1, ERCC4, FANCE, GSTT1, GSTZ1, GTF2H5, KPNA2, MRPS12, MSH5, NFKB1, PTEN, SMARCA4, SND1, SOX4, SUMO1, TARS, TNFRSF10A, TNFSF8, TP53, XPC, and XRCC3 is positively correlated with a likelihood that the patient will exhibit a positive response to a treatment comprising a platinum-based chemotherapy drug. In yet another embodiment of the invention, increased expression level of one or more genes selected from BCL10, BCL2L10, BFAR, BRIP1, CHAF1A, CUL4B, DFFA, IL8, LTBR, MBD2, MBD4, MCM3, MCM4, MCM6, MPG, MSH4, NHEJ1, PRDX4, PTTG1, RAD51L1, RRM1, SHFM1, and TMEM30A is negatively correlated with a likelihood that the patient will exhibit a positive response to a treatment comprising a platinum-based chemotherapy drug, and increased expression level of one or more genes selected from CDKN1A, KPNA2, SUMO1, and TP53 is positively correlated with a likelihood that the patient will exhibit a positive response to treatment comprising a platinum-based chemotherapy drug. In a further embodiment of the invention, a report is generated based on the predicted likelihood of response. 
     The methods of the present invention contemplate determining the expression level of at least one response indicator gene or its gene product. For all aspects of the present invention, the methods may further include determining the expression levels of at least two response indicator genes, or their expression products. It is further contemplated that the methods of the present disclosure may further include determining the expression levels of at least three response indicator genes, or their expression products. It is contemplated that the methods of the present disclosure may further include determining the expression levels of at least four response indicator genes, or their expression products. It is contemplated that the methods of the present disclosure may further include determining the expression levels of at least five response indicator genes, or their expression products. It is contemplated that the methods of the present disclosure may further include determining the expression levels of at least six response indicator genes, or their expression products. It is contemplated that the methods of the present disclosure may further include determining the expression levels of at least seven response indicator genes, or their expression products. It is contemplated that the methods of the present disclosure may further include determining the expression levels of at least eight response indicator genes, or their expression products. It is contemplated that the methods of the present disclosure may further include determining the expression levels of at least nine response indicator genes, or their expression products. The methods may involve determination of the expression levels of at least ten (10) or at least fifteen (15) of the response indicator genes, or their expression products. 
     The expression level, or normalized expression level, of the response indicator gene, or its expression product, is used to predict the likelihood of a positive response. In an embodiment of the invention, a likelihood score (e.g., a score predicting a likelihood of a positive response to treatment with a platinum-based chemotherapy drug) can be calculated based on the expression level or normalized expression level. A score may be calculated using weighted values based on the expression level or normalized expression level of a response indicator gene and its contribution to response to a platinum-based chemotherapy drug. 
     In an embodiment of the invention, the expression product of the response indicator gene to be assayed or measured is an RNA transcript. In one aspect, the RNA transcripts are fragmented. In another embodiment, the expression product is a polypeptide. Determining the expression level of one or more response indicator gene products may be accomplished by, for example, a method of gene expression profiling. The method of gene expression profiling may be, for example, a PCR-based method. The expression level of said genes can be determined, for example, by RT-PCR (reverse transcriptase PCR), quantitative RT-PCR (qRT-PCR), or other PCR-based methods, immunohistochemistry, proteomics techniques, an array-based method, or any other methods known in the art or their combination. 
     The tumor sample may be, for example, a tissue sample containing cancer cells, or portion(s) of cancer cells, where the tissue can be fixed, paraffin-embedded or fresh or frozen tissue. For example, the tissue may be from a biopsy (fine needle, core or other types of biopsy) or obtained by fine needle aspiration, or by obtaining body fluid containing a cancer cell, e.g. urine, blood, etc. In an embodiment of the invention, the tumor sample is obtained from a patient with colorectal cancer. In a specific embodiment of the invention, the patient has stage II (Dukes B) or stage III (Dukes C) colorectal cancer. 
     In another embodiment of the invention, the platinum-based chemotherapy drug is selected from cisplatin, carboplatin, and oxaliplatin. In a particular embodiment, the platinum-based chemotherapy drug is oxaliplatin. Oxaliplatin may be provided alone, or in combination, with one or more additional anti-cancer agents. In a specific embodiment, oxaliplatin is provided in combination with fluorouracil (5-FU) and leucovorin. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIGS. 1A-1B  show the quality control metrics of the siRNA screen.  FIG. 1A  shows the deviation between biological replicates of the siRNA screen by plotting the log 2  fold shift IC 50  of the first replicate against the log 2  fold shift IC 50  of the second replicate, and the R 2  value is as indicated.  FIG. 1B  shows the Z′-factor for each plate in the siRNA screen. 
         FIGS. 2A-2B  show the identification and functional classification of genes modulating HCT116 tumor cell sensitivity to oxaliplatin.  FIG. 2A  shows the results of a 500-gene siRNA screen for genes that modulate sensitivity to oxaliplatin. The median log 2  fold shift in the IC 50  of oxaliplatin following siRNA-treatment is plotted for each gene in the screen. Genes with a median IC 50  shift&gt;median IC 50 ±3 MAD and an RSA P value&lt;0.05 are indicated in large dark circles above 0 log 2  fold shift IC 50  (increased resistance to oxaliplatin) or large dark circles below 0 log 2  fold shift IC 50  (increased sensitivity to oxaliplatin).  FIG. 2B  groups the genes according to biological process using PANTHER®. 
         FIGS. 3A-3B  show the functional classification of genes from the siRNA screen into statistically significant gene subsets.  FIG. 3A  shows the classification of genes from the siRNA screen based on gene ontology (GO) biological processes.  FIG. 3B  shows the classification of genes from the siRNA screen based on the Ingenuity® Pathway Analysis. Threshold for statistical significance is indicated as a horizontal dotted line (p&lt;0.05). 
         FIGS. 4A-4B  show the validation of siRNA knockdown and cDNA overexpression.  FIG. 4A  shows the validation of decreased mRNA following transfection of HCT116 cells with siRNAs targeting the genes identified in the siRNA screen. Plotted is mean±SEM (n=3) fraction of mRNA remaining relative to media-alone treated cells.  FIG. 4B  shows the validation of increased mRNA following transfection of HCT116 cells with full-length LTBR and TMEM30A open reading frames cloned into pCMV-XL4. Plotted is mean±SEM (n=3) fraction of mRNA relative to pCMV-XL4 (empty vector) alone transfected cells. 
         FIGS. 5A-5C  show the validation of genes identified in the siRNA screen for genes regulating sensitivity or resistance to oxaliplatin. The effect of siRNA-silencing or cDNA overexpression on the IC 50  of oxaliplatin was expressed as the log 2  fold-shift of the mean IC 50  of siRNA-treated (or cDNA-overexpressing) cells relative to the mean IC 50  of non-silencing siRNA control-treated (or vector-alone) cells. Cell viability was assayed and IC 50  of oxaliplatin was calculated 72 hrs after cDNA transfection and addition of an 11-point, 2-fold serial dilution of oxaliplatin (50 μM maximum). Data represent mean±SEM (n=3).  FIG. 5A  shows siRNA-silencing of 12 genes from the primary screen in the HCT116 tumor cell line with ON-TARGETplus® siRNAs, each containing pools of 4 siRNAs per target gene.  FIG. 5B  shows the siRNA-silencing of selected genes using the SW480 tumor cell line.  FIG. 5C  shows the effect of cDNA overexpression of full-length LTBR and TMEM30A on the IC 50  of oxaliplatin. 
         FIGS. 6A-6C  show functional analyses of genes modulating sensitivity to oxaliplatin.  FIG. 6A  shows increased levels of DNA damage, as determined by quantification of apurinic/apyrimidinic sites (as % of non-silencing siRNA-treated cells), in CUL4B- and NHEJ1-silenced HCT 116 tumor cells. Cells were transfected, treated with 1.56 μM oxaliplatin, and DNA damage was measured after 72 hr. Dashed line indicates 100% of control. Data represent mean±SEM (n=3); *, P&lt;0.05.  FIG. 6B  shows hierarchical clustering of relative activities of pathway signaling nodes in cells with altered sensitivity to oxaliplatin. The heat map indicates the normalized log 2  ratio of the phosphorylation levels of AKT1 (Ser437), MEK1 (Ser217/222), p38 MAPK (Thr 180/Tyr182), STAT3 (Tyr705), and NFκB p65 (Ser536) in test siRNA-treated cells (+1.56 μM oxaliplatin) relative to non-silencing siRNA-treated cells (+1.56 μM oxaliplatin), as assessed by quantitative analysis using a sandwich ELISA with epitope-specific antibodies 72 hr post transfection and addition of oxaliplatin.  FIG. 6C  shows hierarchical clustering of relative activities of key apoptotic regulators, in cells with altered sensitivity to oxaliplatin. The heat map indicates the normalized log 2  ratio of the phosphorylation levels of p53 (Ser15), and Bad (Ser112), as well as the cleavage status of PARP and Caspase-3 in test siRNA-treated cells (+1.56 μM oxaliplatin) relative to non-silencing siRNA-treated cells (+1.56 μM oxaliplatin), as assessed by quantitative analysis using a sandwich ELISA with epitope-specific antibodies 72 hr post transfection and addition of oxaliplatin. Color bar indicates log 2  of relative activity (phosphorylation or cleavage). 
         FIG. 7  shows alterations in cell cycle distribution in cells with altered sensitivity to oxaliplatin. X-axis indicates DNA content (as determined by propidium iodide staining), and Y-axis indicates cell count. Coding indicates G1, S, or G2/M phases of the cell cycle. Percentages of each stage are indicated (first percentage, G1; second percentage, S; third percentage, G2/M). Cells were transfected, treated with 1.56 μM oxaliplatin, and processed for FACS after 72 hr. 
         FIG. 8  shows a network modeling of the genes in the siRNA screen and shows multiple pathways linked to oxaliplatin sensitivity. Networks of interacting proteins were identified using Ingenuity Pathway Analysis. CDKN1A, KPNA2, SUMO1, and TP53 are genes that exhibited increased resistance to oxaliplatin. The remaining genes shown with filled shapes exhibited increased sensitivity to oxaliplatin. 
     
    
    
     DETAILED DESCRIPTION 
     Definitions 
     Unless defined otherwise, technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Singleton et al.,  Dictionary of Microbiology and Molecular Biology,  2 nd  ed., J. Wiley &amp; Sons (New York, N.Y. 1994), and March,  Advanced Organic Chemistry Reactions, Mechanisms and Structure,  4th ed., J. Wiley &amp; Sons (New York, N.Y. 1992), provide one skilled in the art with a general guide to many of the terms used in the present application. 
     One skilled in the art will recognize many methods and materials similar or equivalent to those described herein that may be used in the practice of the present invention. Indeed, the present invention is in no way limited to the methods and materials described herein. For purposes of the invention, the following terms are defined below. 
     As used herein, the term “amplicon” refers to a piece of DNA that has been synthesized using an amplification technique, such as the polymerase chain reaction (PCR) and ligase chain reaction. 
     The term “anti-cancer agent” as used herein refers to any molecule, compound, chemical, or composition that has an anti-cancer effect, such as a “positive response” as defined below. Anti-cancer agents include, without limitation, chemotherapeutic agents, radiotherapeutic agents, cytokines, anti-angiogenic agents, apoptosis-inducing agents or anti-cancer immunotoxins, such as antibodies. Examples of anti-cancer agents include, without limitation, methotrexate, taxol, mercaptopurine, thioguanine, hydroxyurea, cytarabine, cyclophosphamide, ifosfamide, nitrosoureas, mitomycin, dacarbazine, procarbizine, etoposides, campathecins, bleomycin, doxorubicin, idarubicin, daunorubicin, dactinomycin, plicamycin, mitoxantrone, asparaginase, vinblastine, vincristine, vinorelbine, paclitaxel, docetaxel, fluorouracil (5-FU), and leucovorin. Other anti-cancer agents are known in the art. In an embodiment of the invention, the anti-cancer agent is 5-FU and leucovorin. 
     The terms “assay” or “assaying” as used herein refer to performing a quantitative or qualitative analysis of a component in a sample. The terms include laboratory or clinical observations, and/or measuring the level of the component in the sample. 
     The terms “cancer” and “cancerous” as used herein, refer to or describe the physiological condition that is typically characterized by unregulated cell growth. Examples of cancer in the present application include cancer of the gastrointestinal tract, such as invasive colorectal cancer or Stage II (Dukes B) or Stage III (Dukes C) colorectal cancer. 
     The term “co-expressed” as used herein refers to a statistical correlation between the expression level of one gene and the expression level of another gene. Pairwise co-expression may be calculated by various methods known in the art, e.g., by calculating Pearson correlation coefficients or Spearman correlation coefficient. Co-expressed gene cliques may also be identified using a graph theory. An analysis of co-expression may be calculated using normalized expression data. 
     The terms “colon cancer” and “colorectal cancer” are used interchangeably herein and refer in the broadest sense to (1) all stages and all forms of cancer arising from epithelial cells of the large intestine and/or rectum and/or (2) all stages and all forms of cancer affecting the lining of the large intestine and/or rectum. In the staging systems used for classification of colorectal cancer, the colon and rectum are treated as one organ. 
     The term “correlates” or “correlating” as used herein refers to a statistical association between instances of two events, where events may include numbers, data sets, and the like. For example, when the events involve numbers, a positive correlation (also referred to herein as a “direct correlation”) means that as one increases, the other increases as well. A negative correlation (also referred to herein as an “inverse correlation”) means that as one increases, the other decreases. The present invention provides genes and gene subsets, the expression levels of which are correlated with a particular outcome measure, such as between the expression level of a gene and the likelihood of a positive response to treatment with a drug. For example, the increased expression level of a gene product may be positively correlated with a likelihood of a good clinical outcome for the patient, such as an increased likelihood of long-term survival without recurrence and/or a positive response to a chemotherapy, and the like. Such a positive correlation may be demonstrated statistically in various ways, e.g. by a low hazard ratio. In another example, the increased expression level of a gene product may be negatively correlated with a likelihood of good clinical outcome for the patient. In this case, for example, the patient may have a decreased likelihood of long-term survival without recurrence of the cancer and/or a positive response to a chemotherapy, and the like. Such a negative correlation indicates that the patient likely has a poor prognosis or will respond poorly to a chemotherapy, and this may be demonstrated statistically in various ways, e.g., a high hazard ratio. 
     The term “Ct” as used herein refers to threshold cycle, the cycle number in quantitative polymerase chain reaction (qPCR) at which the fluorescence generated within a reaction well exceeds the defined threshold, i.e. the point during the reaction at which a sufficient number of amplicons have accumulated to meet the defined threshold. 
     The term “expression level” as used herein refers to qualitative or quantitative determination of an expression product or gene product. Expression level may be determined for the RNA expression level of a gene or for the polypeptide expression level of a gene. The term “normalized” expression level as used herein refers to an expression level of a response indicator gene relative to the level of an expression product of a reference gene(s), which might be all measured expression products in the sample, a single reference expression product, or a particular set of expression products. A gene exhibits an “increased expression level” when the expression level of an expression product is higher in a first sample, such as in a clinically relevant subpopulation of patients (e.g., patients who are responsive to a platinum-based chemotherapy drug), than in a second sample, such as in a related subpopulation (e.g., patients who are not responsive to the platinum-based chemotherapy drug). Similarly, a gene exhibits an “increased normalized expression level” when the normalized expression level of an expression product is higher in a first sample, such as in a clinically relevant subpopulation of patients (e.g., patients who are responsive to a platinum-based chemotherapy drug), than in a second sample, such as in a related subpopulation (e.g., patients who are not responsive to the platinum-based cheMotherapy drug). 
     In the context of an analysis of an expression level of a gene in tissue obtained from an individual subject, a gene exhibits “increased expression,” or “increased normalized expression” when the expression level or normalized expression level of the gene in the subject trends toward, or more closely approximates, the expression level or normalized expression level characteristic of a clinically relevant subpopulation of patients. 
     Thus, for example, when the gene analyzed is a gene that shows increased expression in responsive subjects as compared to non-responsive subjects, then “increased expression” or “increased normalized” expression level of a given gene can be described as being positively correlated with a likelihood of a positive response to a platinum-based chemotherapy drug. If the expression level of the gene in the individual subject trends toward a level of expression characteristic of a responsive subject, then the gene expression level supports a determination that the individual subject is more likely to be a responder. If the expression level of the gene in the individual subject trends toward a level of expression characteristic of a non-responsive subject, then the gene expression level supports a determination that the individual subject is more likely to be a non-responder. 
     Similarly, where the gene analyzed is a gene that is increased in expression in non-responsive patients as compared to responsive patients, then “increased expression” or “increased normalized” expression level of a given gene can be described as being negatively correlated with a likelihood of a positive response to a platinum-based chemotherapy drug. If the expression level of the gene in the individual sample trends toward a level of expression characteristic of a non-responsive subject, then the gene expression level supports a determination that the individual patient will more likely to be non-responsive. If the expression level of the gene in the individual sample trends toward a level of expression characteristic of a responsive subject, then the gene expression level supports a determination that the individual patient will more likely to be responsive. 
     Of course, the same meaning can be derived by changing the terms “increased” with “decreased” as long as the association of the relationship between the gene expression level and likelihood of a positive response remains the same. For instance, the phrase “increased expression level of a gene is positively correlated with a likelihood of a positive response” can be rephrased as “decreased expression level of a gene is negatively correlated with a likelihood of a positive response” to mean the same thing. It can also be rephrased to “increased expression level of a gene is negatively correlated with a decreased likelihood of a positive response” to mean the same thing. 
     The term “expression product” or “gene product” are used herein to refer to the RNA transcription products (transcripts) of a gene, including mRNA, and the polypeptide translation products of such RNA transcripts. An expression product may be, for example, an unspliced RNA, an mRNA, a splice variant mRNA, a microRNA, a fragmented RNA, a polypeptide, a post-translationally modified polypeptide, a splice variant polypeptide, etc. 
     The term “long-term” survival is used herein to refer to survival for a particular time period. In an embodiment of the invention, the time period of long-term survival is for at least 3 years. In another embodiment, the time period of long-term survival is for at least 5 years. 
     The term “measuring” as used herein refers to performing a physical act of determining the dimension, quantity, or capacity of a component in a sample. 
     The term “microarray” as used herein refers to an ordered arrangement of hybridizable array elements, e.g., oligonucleotide or polynucleotide probes, on a substrate. 
     The term “polynucleotide” generally refers to any polyribonucleotide or polydeoxyribonucleotide, which may be unmodified RNA or DNA or modified RNA or DNA. Thus, for instance, polynucleotides as used herein include, without limitation, single- and double-stranded DNA, DNA including single- and double-stranded regions, single- and double-stranded RNA, and RNA including single- and double-stranded regions, hybrid molecules comprising DNA and RNA that may be single-stranded or, more typically, double-stranded or include single- and double-stranded regions. In addition, the term “polynucleotide” as used herein refers to triple-stranded regions comprising RNA or DNA or both RNA and DNA. The strands in such regions may be from the same molecule or from different molecules. The regions may include all of one or more of the molecules, but more typically involve only a region of some of the molecules. One of the molecules of a triple-helical region often is an oligonucleotide. The term “polynucleotide” also includes DNAs (including cDNAs) and RNAs and those that contain one or more modified bases. Thus, DNAs or RNAs with backbones modified for stability or for other reasons, are “polynucleotides” as that term is used herein. Moreover, DNAs or RNAs comprising unusual basbs, such as inosine, or modified bases, such as tritiated bases, are included within the term “polynucleotides” as used herein. In general, the term “polynucleotide” embraces all chemically, enzymatically and/or metabolically modified forms of unmodified polynucleotides, as well as the chemical forms of DNA and RNA characteristic of viruses and cells, including simple and complex cells. 
     The term “oligonucleotide” refers to a relatively short polynucleotide, including, without limitation, single-stranded deoxyribonucleotides, single- or double-stranded ribonucleotides, RNA/DNA hybrids and double-stranded DNAs. Oligonucleotides, such as single-stranded DNA probe oligonucleotides, are often synthesized by chemical methods, for example using automated oligonucleotide synthesizers that are commercially available. However, oligonucleotides can be made by a variety of other methods, including in vitro recombinant DNA-mediated techniques and by expression of DNAs in cells and organisms. 
     The term “primer” or “oligonucleotide primer” as used herein, refers to an oligonucleotide that acts to initiate synthesis of a complementary nucleic acid strand when placed under conditions in which synthesis of a primer extension product is induced, e.g., in the presence of nucleotides and a polymerization-inducing agent such as a DNA or RNA polymerase and at suitable temperature, pH, metal ion concentration, and salt concentration. Primers are generally of a length compatible with their use in synthesis of primer extension products, and can be in the range of between about 8 nucleotides and about 100 nucleotides (nt) in length, such as about 10 nt to about 75 nt, about 15 nt to about 60 nt, about 15 nt to about 40 nt, about 18 nt to about 30 nt, about 20 nt to about 40 nt, about 21 nt to about 50 nt, about 22 nt to about 45 nt, about 25 nt to about 40 nt, and so on, e.g., in the range of between about 18 nt and about 40 nt, between about 20 nt and about 35 nt, between about 21 and about 30 nt in length, inclusive, and any length between the stated ranges. Primers can be in the range of between about 10-50 nucleotides long, such as about 15-45, about 18-40, about 20-30, about 21-25 nt and so on, and any length between the stated ranges. In some embodiments, the primers are not more than about 10, 12, 15, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 35, 40, 45, 50, 55, 60, 65, or 70 nucleotides in length. In this context, the term “about” may be construed to mean 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 more nucleotides either 5′ or 3′ from either termini or from both termini. 
     Primers are in many embodiments single-stranded for maximum efficiency in amplification, but may alternatively be double-stranded. If double-stranded, the primer is in many embodiments first treated to separate its strands before being used to prepare extension products. This denaturation step is typically effected by heat, but may alternatively be carried out using alkali, followed by neutralization. Thus, a “primer” is complementary to a template, and complexes by hydrogen bonding or hybridization with the template to give a primer/template complex for initiation of synthesis by a polymerase, which is extended by the covalent addition of bases at its 3′ end. 
     A “primer pair” as used herein refers to first and second primers having nucleic acid sequence suitable for nucleic acid-based amplification of a target nucleic acid. Such primer pairs generally include a first primer having a sequence that is the same or similar to that of a first portion of a target nucleic acid, and a second primer having a sequence that is complementary to a second portion of a target nucleic acid to provide for amplification of the target nucleic acid or a fragment thereof. Reference to “first” and “second” primers herein is arbitrary, unless specifically indicated otherwise. For example, the first primer can be designed as a “forward primer” (which initiates nucleic acid synthesis from a 5′ end of the target nucleic acid) or as a “reverse primer” (which initiates nucleic acid synthesis from a 5′ end of the extension product produced from synthesis initiated from the forward primer). Likewise, the second primer can be designed as a forward primer or a reverse primer. 
     As used herein, the term “probe” or “oligonucleotide probe”, used interchangeably herein, refers to a structure comprised of a polynucleotide, as defined above, that contains a nucleic acid sequence complementary to a nucleic acid sequence present in the target nucleic acid analyte (e.g., a nucleic acid amplification product). The polynucleotide regions of probes may be composed of DNA, and/or RNA, and/or synthetic nucleotide analogs. Probes are generally of a length compatible with their use in specific detection of all or a portion of a target sequence of a target nucleic acid, and are in many embodiments in the range of between about 8 nt and about 100 nt in length, such as about 8 to about 75 nt, about 10 to about 74 nt, about 12 to about 72 nt, about 15 to about 60 nt, about 15 to about 40 nt, about 18 to about 30 nt, about 20 to about 40 nt, about 21 to about 50 nt, about 22 to about 45 nt, about 25 to about 40 nt in length, and so on, e.g., in the range of between about 18-40 nt, about 20-35 nt, or about 21-30 nt in length, and any length between the stated ranges. In some embodiments, a probe is in the range of between about 10-50 nucleotides long, such as about 15-45, about 18-40, about 20-30, about 21-28, about 22-25 and so on, and any length between the stated ranges. In some embodiments, the probes are not more than about 10, 12, 15, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 35, 40, 45, 50, 55, 60, 65, or 70 nucleotides in length. In this context, the term “about” may be construed to mean 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 more nucleotides either 5′ or 3′ from either termini or from both termini. 
     As used herein, the term “pathology” of cancer includes all phenomena that comprise the well-being of the patient. This includes, without limitation, abnormal or uncontrollable cell growth, metastasis, interference with the normal functioning of neighboring cells, release of cytokines or other secretory products at abnormal levels, suppression or aggravation of inflammatory or immunological response, neoplasia, premalignancy, malignancy, invasion of surrounding or distant tissues or organs, such as lymph nodes. 
     The term “platinum-based chemotherapy drug” as used herein refers to a molecule or a composition comprising a molecule containing a coordination complex comprising the chemical element platinum and useful as a chemotherapy drug. Platinum-based chemotherapy drugs generally act by inhibiting DNA synthesis and have some alkylating activity. Examples of platinum-based chemotherapy drugs include cisplatin, carboplatin, and oxaliplatin. Platinum-based chemotherapy drugs encompass those that are currently being used as part of a chemotherapy regimen, those that are currently in development, and those that may be developed in the future. The platinum-based chemotherapy drug may be administered as a monotherapy, or in combination with other anti-cancer agents, or as prodrugs, or together with local therapies such as surgery and radiation, or as adjuvant or neoadjuvant chemotherapy, or as part of a multimodal approach to the treatment of neoplastic disease. For example, oxaliplatin may be administered alone, or in combination with fluorouracil (5-FU) and/or leucovorin for the treatment of colorectal cancer. 
     The term “positive response” as used herein refers to a favorable response to a drug as opposed to an unfavorable response, such as adverse events. A positive response may include, without limitation, (1) inhibition, to some extent, of tumor growth, including slowing down to complete growth arrest; (2) reduction in the number of tumor cells; (3) reduction in tumor size; (4) inhibition (i.e., reduction, slowing down or complete cessation) of tumor cell infiltration into adjacent peripheral organs and/or tissues; (5) inhibition of metastasis; (6) enhancement of anti-tumor immune response, possibly resulting in regression or rejection of the tumor; (7) relief, to some extent, of one or more symptoms associated with the tumor; (8) increase in the length of survival following treatment; and/or (9) decreased mortality at a given point of time following treatment. In individual patients, a positive response can be expressed in terms of a number of clnical parameters, including loss of detectable tumor (complete response, CR), decrease in tumor size and/or cancer cell number (partial response, PR), tumor growth arrest (stable disease, SD), enhancement of anti-tumor immune response, possibly resulting in regression or rejection of the tumor, relief, to some extent, of one or more symptoms associated with the tumor, increase in the length of survival following treatment; and/or decreased mortality at a given point of time following treatment. Continued increase in tumor size and/or cancer cell number and/or tumor metastasis is indicative of lack of a positive response to treatment. 
     In a population, a positive response of a drug can be evaluated on the basis of one or more endpoints. For example, analysis of overall response rate (ORR) classifies as responders those patients who experience CR or PR after treatment with a drug. Analysis of disease control (DC) classifies as responders those patients who experience CR, PR or SD after treatment with drug. 
     The term “progression free survival” as used herein refers to the time interval from treatment of the patient until the progression of cancer or death of the patient, whichever occurs first. 
     The term “responder” as used herein refers to a patient who has cancer, and who exhibits a positive response following treatment with a platinum-based chemotherapy drug. 
     The term “non-responder” as used herein refers to a patient who has cancer, and who has not shown a positive response following treatment with a platinum-based chemotherapy drug. 
     The term “prediction” is used herein to refer to the likelihood that a cancer cell or a cancer patient will have a particular response to treatment, whether positive or negative. In the context of a cancer patient, “prediction” refers to a particular response to treatment following surgical removal of the primary tumor. For example, treatment could include chemotherapy. 
     The predictive methods of the present invention can be used clinically to make treatment decisions by choosing the most appropriate treatment modalities for any particular patient. The predictive methods of the present invention are useful tools in predicting if a patient is likely to exhibit a positive response to a treatment regimen, such as chemotherapy, surgical intervention, or both. 
     The term “reference gene” as used herein refers to a gene whose expression level can be used to compare the expression level of a gene product in a test sample. In an embodiment of the invention, reference genes include housekeeping genes, such as beta-globin, alcohol dehydrogenase, or any other gene, the expression of which does not vary depending on the disease status of the cell containing the gene. In another embodiment, all of the assayed genes or a large subset thereof may serve as reference genes. 
     The term “response indicator gene” as used herein refers to a gene, the expression of which correlates positively or negatively with a positive response to a platinum-based chemotherapy drug, such as oxaliplatin. The expression of a response indicator gene may be determined by assaying or measuring the expression level of an expression product of the response indicator gene. 
     The term “RNA transcript” as used herein refers to the RNA transcription product of a gene, including, for example, mRNA, an unspliced RNA, a splice variant mRNA, a microRNA, and a fragmented RNA. 
     Unless indicated otherwise, each gene name used herein corresponds to the Official Symbol assigned to the gene and provided by Entrez Gene (URL: www.ncbi.nlm.nih.gov/sites/entrez) as of the filing date of this application. 
     The term “tumor sample” as used herein refers to a sample comprising tumor material obtained from a cancerous patient. The term encompasses tumor tissue samples, for example, tissue obtained by surgical resection and tissue obtained by biopsy, such as for example, a core biopsy or a fine needle biopsy. Additionally, the term “tumor sample” encompasses a sample comprising tumor cells obtained from sites other than the primary tumor, e.g., circulating tumor cells. The term also encompasses cells that are the progeny of the patient&#39;s tumor cells, e.g. cell culture samples derived from primary tumor cells or circulating tumor cells. The term further encompasses samples that may comprise protein or nucleic acid material shed from tumor cells in vivo, e.g., bone marrow, blood, plasma, serum, and the like. The term also encompasses samples that have been enriched for tumor cells or otherwise manipulated after their procurement and samples comprising polynucleotides and/or polypeptides that are obtained from a patient&#39;s tumor material. 
     “Stringency” of hybridization reactions is readily determinable by one of ordinary skill in the art, and generally is an empirical calculation dependent upon probe length, washing temperature, and salt concentration. In general, longer probes require higher temperatures for proper annealing, while shorter probes need lower temperatures. Hybridization generally depends on the ability of denatured DNA to re-anneal when complementary strands are present in an environment below their melting temperature. The higher the degree of desired homology between the probe and hybridizable sequence, the higher the relative temperature that can be used. As a result, it follows that higher relative temperatures would tend to make the reaction conditions more stringent, while lower temperatures less so. For additional details and explanation of stringency of hybridization reactions, see Ausubel et al.,  Current Protocols in Molecular Biology , Wiley Interscience Publishers, (1995). 
     “Stringent conditions” or “high stringency conditions”, as defined herein, typically: (1) employ low ionic strength and high temperature for washing, for example 0.015 M sodium chloride/0.0015 M sodium citrate/0.1% sodium dodecyl sulfate at 50° C.; (2) employ during hybridization a denaturing agent, such as formamide, for example, 50% (v/v) formamide with 0.1% bovine serum albumin/0.1% Ficoll/0.1% polyvinylpyrrolidone/50 mM sodium phosphate buffer at pH 6.5 with 750 mM sodium chloride, 75 mM sodium citrate at 42° C.; or (3) employ 50% formamide, 5×SSC (0.75 M NaCl, 0.075 M sodium citrate), 50 mM sodium phosphate (pH 6.8), 0.1% sodium pyrophosphate, 5×Denhardt&#39;s solution, sonicated salmon sperm DNA (50 μg/ml), 0.1% SDS, and 10% dextran sulfate at 42° C., with washes at 42° C. in 0.2×SSC (sodium chloride/sodium citrate) and 50% formamide, followed by a high-stringency wash consisting of 0.1×SSC containing EDTA at 55° C. 
     “Moderately stringent conditions” may be identified as described by Sambrook et al.,  Molecular Cloning: A Laboratory Manual , New York: Cold Spring Harbor Press, 1989, and include the use of washing solution and hybridization conditions (e.g., temperature, ionic strength and % SDS) less stringent that those described above. An example of moderately stringent conditions is overnight incubation at 37° C. in a solution comprising: 20% formamide, 5×SSC (150 mM NaCl, 15 mM trisodium citrate), 50 mM sodium phosphate (pH 7.6), 5×Denhardt&#39;s solution, 10% dextran sulfate, and 20 mg/ml denatured sheared salmon sperm DNA, followed by washing the filters in 1×SSC at about 37-50° C. The skilled artisan will recognize how to adjust the temperature, ionic strength, etc. as necessary to accommodate factors such as probe length and the like. 
     The terms “subject,” “individual,” and “patient” are used interchangeably herein to refer to a mammal being assessed for treatment and/or being treated. In an embodiment, the mammal is a human. The terms “subject,” “individual,” and “patient” thus encompass individuals having cancer (e.g., colorectal cancer or other cancer referenced herein), including those who have undergone or are candidates for resection (surgery) to remove cancerous tissue (e.g., cancerous colorectal tissue or other cancer referenced herein). 
     As used herein, the term “surgery” applies to surgical methods undertaken for removal of cancerous tissue, including resection, laparotomy, colectomy (with or without lymphadenectomy), ablative therapy, endoscopic removal, excision, dissection, and tumor biopsy/removal. The tumor tissue or sections used for gene expression analysis may have been obtained from any of these methods. 
     The terms “threshold” or “thresholding” refer to a procedure used to account for non-linear relationships between gene expression measurements and clinical response as well as to further reduce variation in reported patient scores. When thresholding is applied, all measurements below or above a threshold are set to that threshold value. Non-linear relationship between gene expression and outcome could be examined using smoothers or cubic splines to model gene expression in Cox PH regression on recurrence free interval or logistic regression on recurrence status. Variation in reported patient scores could be examined as a function of variability in gene expression at the limit of quantitation and/or detection for a particular gene. 
     The terms “treatment” and “treating” refer to administering or contacting an agent, or carrying out a procedure (e.g., radiation, a surgical procedure, etc.), for the purpose of obtaining an effect. In a subject, the effect may be prophylactic in terms of completely or partially preventing a disease or symptom thereof and/or may be therapeutic in terms of effecting a partial or complete cure for a disease and/or symptoms of the disease. The terms cover any treatment of a disease in a mammal, particularly in a human, and includes: (a) preventing the disease or a symptom of a disease from occurring in a subject that may be predisposed to the disease but has not yet been diagnosed as having it (e.g., including diseases that may be associated with or caused by a primary disease); (b) inhibiting the disease, i.e., arresting its development; and (c) relieving the disease, i.e., causing regression of the disease. 
     The term “tumor” as used herein, refers to all neoplastic cell growth and proliferation, whether malignant or benign, and all pre-cancerous and cancerous cells and tissues. 
     Two main staging systems are known in the art for colorectal cancer. According to the tumor, node, metastasis (TNM) staging system of the American Joint Committee on Cancer (AJCC) (Green et al. (eds.), ‘ AJCC Cancer Staging Manual,  6 th  ed., Springer: New York, N.Y., 2002), the various stages of colorectal cancer are defined as follows: 
     Tumor: T1: tumor invades submucosal; T2: tumor invades muscularis propria; T3: tumor invades through the muscularis propria into the subserose, or into the pericolic or perirectal tissues; T4: tumor directly invades and/or perforates other organs or structures. 
     Node: N0: no regional lymph node metastasis; N1: metastasis in 1 to 3 regional lymph nodes; N2: metastasis in 4 or more regional lymph nodes. 
     Metastasis: M0: no distant metastasis; M1: distant metastasis present. 
     Stage groupings: Stage I: T1, N0, M0 or T2, N0, M0; Stage II: T3, N0, M0 or T4, N0, M0; Stage III: any T, N1-2, M0; Stage IV: any T, any N, M1. 
     According to the Modified Duke Staging System, the various stages of colorectal cancer are defined as follows: 
     Stage A: the tumor penetrates into the mucosa of the bowel wall but not further. Stage B: tumor penetrates into and through the muscularis propria of the bowel wall. Stage C: tumor penetrates into but not through the muscularis propria of the bowel wall and there is pathologic evidence of colorectal cancer in the lymph nodes; or tumor penetrates into and through the muscularis propria of the bowel wall and there is pathologic evidence of cancer in the lymph nodes. Stage D: tumor has spread beyond the confines of the lymph nodes, into other organs, such as the liver, lung, or bone. 
     The term “computer-based system”, as used herein refers to the hardware means, software means, and data storage means used to analyze information. The minimum hardware of a patient computer-based system comprises a central processing unit (CPU), input means, output means, and data storage means. A skilled artisan can readily appreciate that many of the currently available computer-based system are suitable for use in the present invention and may be programmed to perform the specific measurement and/or calculation functions of the present invention. 
     To “record” data, programming or other information on a computer readable medium refers to a process for storing information, using any such methods as known in the art. Any convenient data storage structure may be chosen, based on the means used to access the stored information. A variety of data processor programs and formats can be used for storage, e.g. word processing text file, database format, etc. 
     A “processor” or “computing means” references any hardware and/or software combination that will perform the functions required of it. For example, any processor herein may be a programmable digital microprocessor such as available in the form of an electronic controller, mainframe, server or personal computer (desktop or portable). Where the processor is programmable, suitable programming can be communicated from a remote location to the processor, or previously saved in a computer program product (such as a portable or fixed computer readable storage medium, whether magnetic, optical or solid state device based). For example, a magnetic medium or optical disk may carry the programming, and can be read by a suitable reader communicating with each processor at its corresponding station. 
     Before the present invention and specific exemplary embodiments of the invention are described, it is to be understood that this invention is not limited to particular embodiments described, as such may, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting, since the scope of the present invention will be limited only by the appended claims. 
     Where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limit of that range and any other stated or intervening value in that stated range is encompassed within the invention. The upper and lower limits of these smaller ranges may independently be included in the smaller ranges is also encompassed within the invention, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either both of those included limits are also included in the invention. 
     As used herein and in the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “a reference gene” includes a plurality of such genes and reference to “a platinum-based chemotherapy drug” includes reference to one or more platinum-based chemotherapy drug, and so forth. 
     DETAILED DESCRIPTION 
     The practice of the methods and compositions of the present disclosure will employ, unless otherwise indicated, conventional techniques of molecular biology (including recombinant techniques), microbiology, cell biology, and biochemistry, which are within the skill of the art. Such techniques are explained fully in the literature, such as, “ Molecular Cloning: A Laboratory Manual”,  2nd edition (Sambrook et al., 1989); “ Oligonucleotide Synthesis ” (M. J. Gait, ed., 1984); “ Animal Cell Culture ” (R. I. Freshney, ed., 1987); “ Methods in Enzymology ” (Academic Press, Inc.); “ Handbook of Experimental Immunology”,  4th edition (D. M. Weir &amp; C. C. Blackwell, eds., Blackwell Science Inc., 1987); “ Gene Transfer Vectors for Mammalian Cells ” (J. M. Miller &amp; M. P. Calos, eds., 1987); “ Current Protocols in Molecular Biology ” (F. M. Ausubel et al., eds., 1987); and “ PCR: The Polymerase Chain Reaction ”, (Mullis et al., eds., 1994). 
     The present invention provides response indicator genes of platinum-based chemotherapy drugs. These genes are listed in Tables 1-4. The response indicator genes may be further grouped into gene subsets, depending on their known function. For example, the gene subsets may include a “drug resistance group,” “drug transporter group,” “apoptosis group,” “DNA damage repair group,” “cell cycle group,” “p53 pathway group,” and “nucleotide excision repair (NER) group.” Table 1 indicates which gene subset in which each gene may be grouped. The present invention further provides methods for determining genes that co-express with the response indicator genes. The co-expressed genes themselves are useful response indicator genes. The co-expressed genes may be substituted for the response indicator gene with which they co-express. 
     The present invention provides a number of methods that utilize the response indicator genes and associated information. In a first aspect, the present invention provides a method of determining whether a cancer cell is likely to exhibit a positive response to a platinum-based chemotherapy drug. In another aspect, the present invention provides a method of predicting a likelihood that a patient with cancer will exhibit a positive response to a treatment comprising a platinum-based chemotherapy drug. The methods of the invention comprise assaying or measuring the expression level of the response indicator gene(s) in a sample comprising cancer cells or in a tumor sample, and determining the likelihood of a positive response based on the correlation between the expression level of the response indicator gene(s) and a positive response to the platinum-based chemotherapy drug. 
     The response indicator genes and associated information provided by the present invention also have utility in the development of therapies to treat cancers and screening patients for inclusion in clinical trials that test the efficacy of platinum-based chemotherapy drugs. The response indicator genes and associated information may further be used to design or produce a reagent that modulates the level or activity of the expression product. Such reagents may include, but are not limited to, an antisense RNA, a small inhibitory RNA (siRNA), a ribozyme, a small molecule, a monoclonal antibody, and a polyclonal antibody. 
     In various embodiments of the methods of the present invention, various technological approaches are available for assaying or measuring the expression levels of the response indicator genes, including, without limitation, RT-PCR, microarrays, serial analysis of gene expression (SAGE), and nucleic acid sequence, which are described in more detail below. 
     Correlating Expression Level of a Response Indicator Gene Product to a Positive Response to a Platinum-Based Chemotherapy Drug 
     One skilled in the art will recognize that there are many statistical methods that may be used to determine whether there is a correlation between an outcome of interest (e.g., likelihood of survival, likelihood of response to chemotherapy) and expression levels of a gene product as described here. This relationship can be presented as a continuous recurrence score (R S ), or patients may be stratified into risk groups (e.g., low, intermediate, high). For example, a Cox proportional hazards regression model may fit to a particular clinical endpoint (e.g., RFI, DFS, OS). One assumption of the Cox proportional hazards regression model is the proportional hazards assumption, i.e. the assumption that effect parameters multiply the underlying hazard. Assessments of model adequacy may be performed including, but not limited to, examination of the cumulative sum of martingale residuals. One skilled in the art would recognize that there are numerous statistical methods that may be used (e.g., Royston and Parmer (2002), smoothing spline, etc.) to fit a flexible parametric model using the hazard scale and the Weibull distribution with natural spline smoothing of the log cumulative hazards function, with effects for treatment (chemotherapy or observation) and R S  allowed to be time-dependent. (See, e.g., P. Royston, M. Parmer,  Statistics in Medicine  21(15:2175-2197 (2002).) 
     Many statistical methods may be used to determine if there is a correlation between expression levels of response indicator genes and positive response to treatment. For example, this relationship can be presented as a continuous treatment score (TS), or patients may stratified into benefit groups (e.g., low, intermediate, high). The interaction studied may vary, e.g. standard of care vs. new treatment, or surgery alone vs. surgery followed by chemotherapy. For example, a Cox proportional hazards regression could be used to model the follow-up data, i.e. censoring time to recurrence at a certain time (e.g., 3 years) after randomization for patients who have not experienced a recurrence before that time, to determine if the TS is associated with the magnitude of chemotherapy benefit. One might use the likelihood ratio test to compare the reduced model with RS, TS and the treatment main effect, with the full model that includes RS, TS, the treatment main effect, and the interaction of treatment and TS. A pre-determined p-value cut-off (e.g., p&lt;0.05) may be used to determine significance. 
     Alternatively, the method of Royston and Parmer (2002) can be used to fit a flexible parametric model using the hazard scale and the Weibull distribution with natural spline smoothing of the log cumulative hazards function, with effects for treatment (chemotherapy or observation), RS, TS and the interaction of TS with treatment, allowing the effects of RS, TS and TS interaction with treatment to be time dependent. To assess relative chemotherapy benefit across the benefit groups, pre-specified cut-points for the RS and TS may be used to define low, intermediate, and high chemotherapy benefit groups. The relationship between treatment and (1) benefit groups; and (2) clinical/pathologic covariates may also be tested for significance. For example, one skilled in the art could identify significant trends in absolute chemotherapy benefit for recurrence at 3 years across the low, intermediate, and high chemotherapy benefit groups for surgery alone or surgery followed by chemotherapy groups. An absolute benefit of at least 3-6% in the high chemotherapy benefit group would be considered clinically significant. 
     In an exemplary embodiment, power calculations are carried out for the Cox proportional hazards model with a single non-binary covariate using the method proposed by F. Hsieh and P. Lavori,  Control Clin Trials  21:552-560 (2000) as implemented in PASS 2008. 
     Any of the methods described may group the expression levels of response indicator genes. The grouping of genes may be performed at least in part based on knowledge of the contribution of the genes according to physiologic functions or component cellular characteristics, such as in the gene subsets described herein. The formation of groups, in addition, can facilitate the mathematical weighting of the contribution of various expression levels to the recurrence and/or treatment scores. The weighting of a gene group representing a physiological process or component cellular characteristic can reflect the contribution of that process or characteristic to the pathology of the cancer and clinical outcome. Accordingly, the present invention provides gene subsets of the response indicator genes identified herein for use in the methods disclosed herein. 
     The response indicator genes of platinum-based chemotherapy drugs of the present invention are listed in Tables 1-4. In an embodiment of the invention, increased expression level of one or more genes selected from ATP6V0C, BCL10, BCL2L10, BFAR, BRIP1, CARD6, CCND1, CDC20, CDC25A, CFLAR, CHAF 1A, CRADD, CUL4B, DFFA, E2F2, E2F4, E2F6, GADD45B, HMG20B, IL8, LTBR, MBD2, MBD3, MBD4, MCM3, MCM4, MCM6, MGST3, MPG, MRPL3, MSH4, NHEJ1, OGT, PAICS, PPP2R5C, PRDX4, PTTG1, RAD51L1, RARA, RBM4, RECQL, RRM1, SHFM1, SPO11, TMEM30A, UBE2A, UBE2S, XAB2, and XRCC2 is negatively correlated with a likelihood of a positive response to a platinum-based chemotherapy drug. 
     In another embodiment of the invention, increased expression level of one or more genes selected from ABL1, APAF1, BAX, CARD4, CASP5, CCT5, CDKN1A, CDKN3, CIDEA, CRIP2, CUL1, CYP1A2, DNMT1, ERCC4, FANCE, GSTT1, GSTZ1, GTF2H5, KPNA2, MRPS12, MSH5, NFKB1, PTEN, SMARCA4, SND1, SOX4, SUMO1, TARS, TNFRSF10A, TNFSF8, TP53, XPC, and XRCC3 is positively correlated with a likelihood of a positive response to a platinum-based chemotherapy drug. 
     In a specific embodiment of the invention, increased expression level of one or more genes selected from BCL10, BCL2L10, BFAR, BRIP1, CHAF1A, CUL4B, DFFA, IL8, LTBR, MBD2, MBD4, MCM3, MCM4, MCM6, MPG, MSH4, NHEJ1, PRDX4, PTTG1, RAD51 L1, RRM1, SHFM1, and TMEM30A is negatively correlated with a likelihood of a positive response to platinum-based chemotherapy drug, and increased expression level of one or more genes selected from CDKN1A, KPNA2, SUMO1, and TP53 is positively correlated with a likelihood of a positive response to a platinum-based chemotherapy drug. 
     In a particular embodiment of the invention, the platinum-based chemotherapy drug is oxaliplatin and the response indicator gene(s) is assayed or measured in colorectal cancer cells. Oxaliplatin may be provided in combination with one or more anti-cancer agents, such as 5-FU and leucovorin. The colorectal cancer cells may be a tumor sample obtained from a human patient with colorectal cancer, such as stage II (Dukes B) or stage III (Dukes C) colorectal cancer. In another embodiment, the expression level of the response indicator gene(s) is normalized as described in more detail below. 
     Thus, in an embodiment of the invention, increased expression level of one or more genes selected from ATP6V0C, BCL10, BCL2L10, BFAR, BRIP1, CARD6, CCND1, CDC20, CDC25A, CFLAR, CHAF1A, CRADD, CUL4B, DFFA, E2F2, E2F4, E2F6, GADD45B, HMG20B, IL8, LTBR, MBD2, MBD3, MBD4, MCM3, MCM4, MCM6, MGST3, MPG, MRPL3, MSH4, NHEJ1, OGT, PAICS, PPP2R5C, PRDX4, PTTG1, RAD51L1, RARA, RBM4, RECQL, RRM1, SHFM1, SPO11, TMEM30A, UBE2A, UBE2S, XAB2, and XRCC2 is negatively correlated with a likelihood of a positive response to oxaliplatin in colorectal cancer cells or in a human patient with colorectal cancer, such as such as stage II (Dukes B) or stage III (Dukes C) colorectal cancer. 
     In another embodiment of the invention, increased expression level of one or more genes selected from ABL1, APAF1, BAX, CARD4, CASP5, CCT5, CDKN1A, CDKN3, CIDEA, CRIP2, CUL1, CYP1A2, DNMT1, ERCC4, FANCE, GSTT1, GSTZ1, GTF2H5, KPNA2, MRPS12, MSH5, NFKB1, PTEN, SMARCA4, SND1, SOX4, SUMO1, TARS, TNFRSF10A, TNFSF8, TP53, XPC, and XRCC3 is positively correlated with a likelihood of a positive response to oxaliplatin in colorectal cancer cells or in a human patient with colorectal cancer, such as such as stage II (Dukes B) or stage III (Dukes C) colorectal cancer. 
     In a particular embodiment of the invention, increased expression level of one or more genes selected from BCL10, BCL2L10, BFAR, BRIP1, CHAF1A, CUL4B, DFFA, IL8, LTBR, MBD2, MBD4, MCM3, MCM4, MCM6, MPG, MSH4, NHEJ1, PRDX4, PTTG1, RAD51L1, RRM1, SHFM1, and TMEM30A is negatively correlated with a likelihood of a positive response to oxaliplatin in colorectal cancer cells or in a human patient with colorectal cancer, such as stage II (Dukes B) or stage III (Dukes C) colorectal cancer. In another embodiment, increased expression level of one or more genes selected from CDKN1A, KPNA2, SUMO1, and TP53 is positively correlated with a likelihood of a positive response to oxaliplatin in colorectal cancer cells or in a human patient with colorectal cancer, such as stage II (Dukes B) or stage III (Dukes C) colorectal cancer. 
     Methods to Predict Likelihood of a Positive Response to a Platinum-Based Chemotherapy Drug 
     As described above, a number of response indicator genes were identified. Expression levels or normalized expression levels of these indicator gene products can then be determined in cancer cells or in a tumor sample obtained from an individual patient who has cancer and for whom treatment with a platinum-based chemotherapy drug is being contemplated. Depending on the outcome of the assessment, treatment with a platinum-based chemotherapy drug may be indicated, or an alternative treatment regimen may be indicated. 
     In carrying out the method of the present invention, cancer cells or a tumor sample is assayed or measured for an expression level of a response indicator gene product(s). The tumor sample can be obtained from a solid tumor, e.g., via biopsy, or from a surgical procedure carried out to remove a tumor; or from a tissue or bodily fluid that contains cancer cells. In an embodiment of the invention, the tumor sample is obtained from a patient with colorectal cancer, such as stage II (Duke&#39;s B) or stage III (Duke&#39;s C) colorectal cancer. In another embodiment, the expression level of a response indicator gene is normalized relative to the level of an expression product of one or more reference genes. In a particular embodiment of the invention, the platinum-based chemotherapy drug is oxaliplatin. Oxaliplatin may be provided in combination with one or more anti-cancer agents, such as 5-FU and leucovorin 
     The likelihood of a positive response to treatment with a platinum-based chemotherapy drug in an individual patient is predicted by comparing, directly or indirectly, the expression level or normalized expression level of the response indicator gene in the tumor sample from the individual patient to the expression level or normalized expression level of the response indicator gene in a clinically relevant subpopulation of patients. Thus, as explained above, when the response indicator gene analyzed is a gene that shows increased expression in responsive subjects as compared to non-responsive subjects, then if the expression level of the gene in the individual subject trends toward a level of expression characteristic of a responsive subject, then the gene expression level supports a determination that the individual subject is more likely to be a responder. Similarly, where the response indicator gene analyzed is a gene that is increased in expression in non-responsive patients as compared to responsive patients, then if the expression level of the gene in the individual subject trends toward a level of expression characteristic of a non-responsive subject, then the gene expression level supports a determination that the individual patient will more likely to be non-responsive. Thus, increased expression or increased normalized expression level of a given gene can be described as being positively correlated with a likelihood of a positive response to a platinum-based chemotherapy drug, or as being negatively correlated with a likelihood of a positive response to a platinum-based chemotherapy drug. 
     It is understood that the expression level or normalized expression level of a response indicator gene from an individual patient can be compared, directly or indirectly, to the expression level or normalized expression level of the response indicator gene in a clinically relevant subpopulation of patients. For example, when compared indirectly, the expression level or normalized expression level of the response indicator gene from the individual patient may be used to calculate a likelihood of a positive response, such as a recurrence score (R S ) or treatment score (TS) as described above, and compared to a calculated score in the clinically relevant subpopulation of patients. 
     It is also understood that it can be useful to measure the expression level of a response indicator gene product at multiple time points, for example, prior to and during the course of treatment with a platinum-based chemotherapy drug. For example, an initial assessment of the likelihood that a patient will respond to treatment with a platinum-based chemotherapy drug can be made prior to initiation of treatment in order to optimize treatment choice. 
     Development of drug resistance is a well-known phenomenon in chemotherapeutic treatment of cancer patients. As they proliferate, tumor cells can accumulate mutations that confer drug resistance through a variety of mechanisms, including resistance to a platinum-based chemotherapy drug. Tests that utilize the measurement of response indicator genes to assess the likelihood of a positive response can be carried out at time intervals to monitor changes indicative of the onset of drug resistance that may arise from changes in the tumor over time. It is not necessary to know what mutations or changes have taken place in the tumor in order to monitor consequent changes in the gene expression level of response indicator genes and assess the likelihood of a continuing positive response. 
     Methods of Assaying Expression Levels of a Gene Product 
     The methods and compositions of the present disclosure will employ, unless otherwise indicated, conventional techniques of molecular biology (including recombinant techniques), microbiology, cell biology, and biochemistry, which are within the skill of the art. Exemplary techniques are explained in the literature, such as, “ Molecular Cloning: A Laboratory Manual”,  2 nd  edition (Sambrook et al., 1989); “Oligonucleotide Synthesis” (M. J. Gait, ed., 1984); “ Animal Cell Culture ” (R. I. Freshney, ed., 1987); “ Methods in Enzymology ” (Academic Press, Inc.); “ Handbook of Experimental Immunology”,  4 th  edition (D. M. Weir &amp; C. C. Blackwell, eds., Blackwell Science Inc., 1987); “ Gene Transfer Vectors for Mammalian Cells”  (J. M. Miller &amp; M. P. Calos, eds., 1987); “ Current Protocols in Molecular Biology”  (F. M. Ausubel et al., eds., 1987); and “ PCR: The Polymerase Chain Reaction ” (Mullis et al., eds., 1994). 
     Methods of gene expression profiling include methods based on hybridization analysis of polynucleotides, methods based on sequencing of polynucleotides, and proteomics-based methods. Exemplary methods known in the art for the quantification of mRNA expression in a sample include northern blotting and in situ hybridization (Parker &amp; Barnes,  Methods in Molecular Biology  106:247-283 (1999)); RNAse protection assays (Hod,  Biotechniques  13:852-854 (1992)); and PCR-based methods, such as reverse transcription PCT (RT-PCR) (Weis et al.,  Trends in Genetics  8:263-264 (1992)). Antibodies may be employed that can recognize sequence-specific duplexes, including DNA duplexes, RNA duplexes, and DNA-RNA hybrid duplexes or DNA-protein duplexes. Representative methods for sequencing-based gene expression analysis include Serial Analysis of Gene Expression (SAGE), and gene expression analysis by massively parallel signature sequencing (MPSS). 
     Reverse Transcriptase PCR(RT-PCR) 
     Typically, mRNA is isolated from a sample. The starting material is typically total RNA isolated from a human tumor, usually from a primary tumor. Optionally, normal tissues from the same patient can be used as an internal control. mRNA can be extracted from a tissue sample, e.g., from a sample that is fresh, frozen (e.g. fresh frozen), or paraffin-embedded and fixed (e.g. formalin-fixed). 
     General methods for mRNA extraction are well known in the art and are disclosed in standard textbooks of molecular biology, including Ausubel et al.,  Current Protocols of Molecular Biology,  John Wiley and Sons (1997). Methods for RNA extraction from paraffin embedded tissues are disclosed, for example, in Rupp and Locker,  Lab Invest.  56:A67 (1987), and De Andrés et al.,  BioTechniques  18:42044 (1995). In particular, RNA isolation can be performed using a purification kit, buffer set and protease from commercial manufacturers, such as Qiagen, according to the manufacturer&#39;s instructions. For example, total RNA from cells in culture can be isolated using Qiagen RNeasy mini-columns. Other commercially available RNA isolation kits include MasterPure™ Complete DNA and RNA Purification Kit (EPICENTRE®, Madison, Wis.), and Paraffin Block RNA Isolation Kit (Ambion, Inc.). Total RNA from tissue samples can be isolated using RNA Stat-60 (Tel-Test). RNA prepared from a tumor sample can be isolated, for example, by cesium chloride density gradient centrifugation. 
     The sample containing the RNA is then subjected to reverse transcription to produce cDNA from the RNA template, followed by exponential amplification in a PCR reaction. The two most commonly used reverse transcriptases are avian myeloblastosis virus reverse transcriptase (AMV-RT) and Moloney murine leukemia virus reverse transcriptase (MMLV-RT). The reverse transcription step is typically primed using specific primers, random hexamers, or oligo-dT primers, depending on the circumstances and the goal of expression profiling. For example, extracted RNA can be reverse-transcribed using a GeneAmp RNA PCR kit (Perkin Elmer, Calif., USA), following the manufacturer&#39;s instructions. The derived cDNA can then be used as a template in the subsequent PCR reaction. 
     PCR-based methods use a thermostable DNA-dependent DNA polymerase, such as a Taq DNA polymerase. For example, TaqMan® PCR typically utilizes the 5′-nuclease activity of Taq or Tth polymerase to hydrolyze a hybridization probe bound to its target amplicon, but any enzyme with equivalent 5′ nuclease activity can be used. Two oligonucleotide primers are used to generate an amplicon typical of a PCR reaction product. A third oligonucleotide, or probe, can be designed to facilitate detection of a nucleotide sequence of the amplicon located between the hybridization sites of the two PCR primers. The probe can be detectably labeled, e.g., with a reporter dye, and can further be provided with both a fluorescent dye, and a quencher fluorescent dye, as in a Taqman® probe configuration. Where a Taqman® probe is used, during the amplification reaction, the Taq DNA polymerase enzyme cleaves the probe in a template-dependent manner. The resultant probe fragments disassociate in solution, and signal from the released reporter dye is free from the quenching effect of the second fluorophore. One molecule of reporter dye is liberated for each new molecule synthesized, and detection of the unquenched reporter dye provides the basis for quantitative interpretation of the data. 
     TaqMan® RT-PCR can be performed using commercially available equipment, such as, for example, ABI PRISM 7700™ Sequence Detection System™ (Perkin-Elmer-Applied Biosystems, Foster City, Calif., USA), or Lightcycler (Roche Molecular Biochemicals, Mannheim, Germany). In a preferred embodiment, the 5′ nuclease procedure is run on a real-time quantitative PCR device such as the ABI PRISM 7700™ Sequence Detection System™. The system consists of a thermocycler, laser, charge-coupled device (CCD), camera and computer. The system amplifies samples in a 384-well format on a thermocycler. The RT-PCR may be performed in triplicate wells with an equivalent of 2 ng RNA input per 10 μL-reaction volume. During amplification, laser-induced fluorescent signal is collected in real-time through fiber optics cables for all wells, and detected at the CCD. The system includes software for running the instrument and for analyzing the data. 
     5′-Nuclease assay data are generally initially expressed as a threshold cycle (“C t ”). Fluorescence values are recorded during every cycle and represent the amount of product amplified to that point in the amplification reaction. The threshold cycle (C t ) is generally described as the point when the fluorescent signal is first recorded as statistically significant. 
     To minimize errors and the effect of sample-to-sample variation, RT-PCR is usually performed using an internal standard. The ideal internal standard gene (also referred to as a reference gene) is expressed at a constant level among cancerous and non-cancerous tissue of the same origin (i.e., a level that is not significantly different among normal and cancerous tissues), and is not significantly affected by the experimental treatment (i.e., does not exhibit a significant difference in expression level in the relevant tissue as a result of exposure to chemotherapy). For example, reference genes useful in the methods disclosed herein should not exhibit significantly different expression levels in cancerous colon as compared to normal colon tissue. RNAs most frequently used to normalize patterns of gene expression are mRNAs for the housekeeping genes glyceraldehyde-3-phosphate-dehydrogenase (GAPDH) and β-actin. Exemplary reference genes used for normalization comprise one or more of the following genes: ATP5E, GPX1, PGK1, UBB, and VDAC2. Gene expression measurements can be normalized relative to the mean of one or more (e.g., 2, 3, 4, 5, or more) reference genes. Reference-normalized expression measurements can range from 0 to 15, where a one unit increase generally reflects a 2-fold increase in RNA quantity. 
     Real time PCR is compatible both with quantitative competitive PCR, where an internal competitor for each target sequence is used for normalization, and with quantitative comparative PCR using a normalization gene contained within the sample, or a housekeeping gene for RT-PCR. For further details see, e.g. Held et al.,  Genome Research  6:986-994 (1996). 
     The steps of a representative protocol for use in the methods of the present disclosure use fixed, paraffin-embedded tissues as the RNA source. mRNA isolation, purification, primer extension and amplification can be preformed according to methods available in the art. (see, e.g., Godfrey et al.  J. Molec. Diagnostics  2: 84-91 (2000); Specht et al.,  Am. J. Pathol.  158: 419-29 (2001)). Briefly, a representative process starts with cutting about 10 μM thick sections of paraffin-embedded tumor tissue samples. The RNA is then extracted, and protein and DNA are depleted from the RNA-containing sample. After analysis of the RNA concentration, RNA is reverse transcribed using gene specific primers followed by RT-PCR to provide for cDNA amplification products. 
     Design of PCR Primers and Probes 
     PCR primers and probes can be designed based upon exon or intron sequences present in the mRNA transcript of the gene of interest. Primer/probe design can be performed using publicly available software, such as the DNA BLAT software developed by Kent, W. J.,  Genome Res.  12(4):656-64 (2002), or by the BLAST software including its variations. 
     Where necessary or desired, repetitive sequences of the target sequence can be masked to mitigate non-specific signals. Exemplary tools to accomplish this include the Repeat Masker program available on-line through the Baylor College of Medicine, which screens DNA sequences against a library of repetitive elements and returns a query sequence in which the repetitive elements are masked. The masked sequences can then be used to design primer and probe sequences using any commercially or otherwise publicly available primer/probe design packages, such as Primer Express (Applied Biosystems); MGB assay-by-design (Applied Biosystems); Primer3 (Steve Rozen and Helen J. Skaletsky (2000) Primer3 on the WWW for general users and for biologist programmers. In: Rrawetz S, Misener S (eds) Bioinformatics  Methods and Protocols: Methods in Molecular Biology . Humana Press, Totowa, N. J., pp 365-386). 
     Other factors that can influence PCR primer design include primer length, melting temperature (Tm), and G/C content, specificity, complementary primer sequences, and 3′-end sequence. In general, optimal PCR primers are generally 17-30 bases in length, and contain about 20-80%, such as, for example, about 50-60% G+C bases, and exhibit Tm&#39;s between 50 and 80° C., e.g. about 50 to 70° C. 
     For further guidelines for PCR primer and probe design see, e.g. Dieffenbach, C W. et al, “General Concepts for PCR Primer Design” in:  PCR Primer, A Laboratory Manual , Cold Spring Harbor Laboratory Press, New York, 1995, pp. 133-155; Innis and Gelfand, “Optimization of PCRs” in:  PCR Protocols, A Guide to Methods and Applications , CRC Press, London, 1994, pp. 5-11; and Plasterer, T. N.  Primerselect: Primer and probe design . Methods Mol. Biol. 70:520-527 (1997), the entire disclosures of which are hereby expressly incorporated by reference. 
     Table 1 provides the GeneBank accession numbers and Entrez ID numbers for each of the response indicator genes of the invention. Based on these sequences, primers, probes, and amplicon sequences can be determined using methods known in the art. 
     MassARRAY® System 
     In MassARRAY-based methods, such as the exemplary method developed by Sequenom, Inc. (San Diego, Calif.) following the isolation of RNA and reverse transcription, the obtained cDNA is spiked with a synthetic DNA molecule (competitor), which matches the targeted cDNA region in all positions, except a single base, and serves as an internal standard. The cDNA/competitor mixture is PCR amplified and is subjected to a post-PCR shrimp alkaline phosphatase (SAP) enzyme treatment, which results in the dephosphorylation of the remaining nucleotides. After inactivation of the alkaline phosphatase, the PCR products from the competitor and cDNA are subjected to primer extension, which generates distinct mass signals for the competitor- and cDNA-derived PCR products. After purification, these products are dispensed on a chip array, which is pre-loaded with components needed for analysis with matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis. The cDNA present in the reaction is then quantified by analyzing the ratios of the peak areas in the mass spectrum generated. For further details see, e.g. Ding and Cantor,  Proc. Natl. Acad. Sci. USA  100:3059-3064 (2003). 
     Other PCR-Based Methods 
     Further PCR-based techniques that can find use in the methods disclosed herein include, for example, BeadArray® technology (Illumina, San Diego, Calif.; Oliphant et al.,  Discovery of Markers for Disease  (Supplement to Biotechniques), June 2002; Ferguson et al.,  Analytical Chemistry  72:5618 (2000)); BeadsArray for Detection of Gene Expression® (BADGE), using the commercially available LuminexlOO LabMAP® system and multiple color-coded microspheres (Luminex Corp., Austin, Tex.) in a rapid assay for gene expression (Yang et al.,  Genome Res.  11:1888-1898 (2001)); and high coverage expression profiling (HiCEP) analysis (Fukumura et al.,  Nucl. Acids. Res.  31(16) e94 (2003). 
     Microarrays 
     Expression levels of a gene of interest can also be assessed using the microarray technique. In this method, polynucleotide sequences of interest (including cDNAs and oligonucleotides) are arrayed on a substrate. The arrayed sequences are then contacted under conditions suitable for specific hybridization with detectably labeled cDNA generated from mRNA of a sample. As in the RT-PCR method, the source of mRNA typically is total RNA isolated from a tumor sample, and optionally from normal tissue of the same patient as an internal control or cell lines. mRNA can be extracted, for example, from frozen or archived paraffin-embedded and fixed (e.g. formalin-fixed) tissue samples. 
     For example, PCR amplified inserts of cDNA clones of a gene to be assayed are applied to a substrate in a dense array. Usually at least 10,000 nucleotide sequences are applied to the substrate. For example, the microarrayed genes, immobilized on the microchip at 10,000 elements each, are suitable for hybridization under stringent conditions. Fluorescently labeled cDNA probes may be generated through incorporation of fluorescent nucleotides by reverse transcription of RNA extracted from tissues of interest. Labeled cDNA probes applied to the chip hybridize with specificity to each spot of DNA on the array. After washing under stringent conditions to remove non-specifically bound probes, the chip is scanned by confocal laser microscopy or by another detection method, such as a CCD camera. Quantitation of hybridization of each arrayed element allows for assessment of corresponding mRNA abundance. 
     With dual color fluorescence, separately labeled cDNA probes generated from two sources of RNA are hybridized pair wise to the array. The relative abundance of the transcripts from the two sources corresponding to each specified gene is thus determined simultaneously. The miniaturized scale of the hybridization affords a convenient and rapid evaluation of the expression pattern for large numbers of genes. Such methods have been shown to have the sensitivity required to detect rare transcripts, which are expressed at a few copies per cell, and to reproducibly detect at least approximately two-fold differences in the expression levels (Schena et at,  Proc. Natl. Acad. Sci. USA  93(2):106-149 (1996)). Microarray analysis can be performed on commercially available equipment, following the manufacturer&#39;s protocols, such as by using the Affymetrix GenChip® technology, or Incyte&#39;s microarray technology. 
     Serial Analysis of Gene Expression (SAGE) 
     Serial analysis of gene expression (SAGE) is a method that allows the simultaneous and quantitative analysis of a large number of gene transcripts, without the need of providing an individual hybridization probe for each transcript. First, a short sequence tag (about 10-14 bp) is generated that contains sufficient information to uniquely identify a transcript, provided that the tag is obtained from a unique position within each transcript. Then, many transcripts are linked together to form long serial molecules, that can be sequenced, revealing the identity of the multiple tags simultaneously. The expression pattern of any population of transcripts can be quantitatively evaluated by determining the abundance of individual tags, and identifying the gene corresponding to each tag. For more details see, e.g. Velculescu et al.,  Science  270:484-487 (1995); and Velculescu et al.,  Cell  88:243-51 (1997). 
     Gene Expression Analysis by Nucleic Acid Sequencing 
     Nucleic acid sequencing technologies are suitable methods for analysis of gene expression. The principle underlying these methods is that the number of times a cDNA sequence is detected in a sample is directly related to the relative expression of the mRNA corresponding to that sequence. These methods are sometimes referred to by the term Digital Gene Expression (DGE) to reflect the discrete numeric property of the resulting data. Early methods applying this principle were Serial Analysis of Gene Expression (SAGE) and Massively Parallel Signature Sequencing (MPSS). See, e.g., S. Brenner, et al.,  Nature Biotechnology  18(6):630-634 (2000). More recently, the advent of “next-generation” sequencing technologies has made DGE simpler, higher throughput, and more affordable. As a result, more laboratories are able to utilize DGE to screen the expression of more genes in more individual patient samples than previously possible. See, e.g., J. Marioni,  Genome Research  18(9):1509-1517 (2008); R. Morin,  Genome Research  18(4):610-621 (2008); A. Mortazavi,  Nature Methods  5(7):621-628 (2008); N. Cloonan,  Nature Methods  5(7):613-619 (2008). 
     Isolating RNA from Body Fluids 
     Methods of isolating RNA for expression analysis from blood, plasma and serum (see for example, Tsui N B et al. (2002)  Clin. Chem.  48, 1647-53 and references cited therein) and from urine (see for example, Boom R et al. (1990)  J Clin Microbiol.  28, 495-503 and reference cited therein) have been described. 
     Immunohistochemistry 
     Immunohistochemistry methods are also suitable for detecting the expression levels of genes and applied to the method disclosed herein. Antibodies (e.g., monoclonal antibodies) that specifically bind a gene product of a gene of interest can be used in such methods. The antibodies can be detected by direct labeling of the antibodies themselves, for example, with radioactive labels, fluorescent labels, hapten labels such as biotin, or an enzyme such as horse radish peroxidase or alkaline phosphatase. Alternatively, unlabeled primary antibody can be used in conjunction with a labeled secondary antibody specific for the primary antibody. Immunohistochemistry protocols and kits are well known in the art and are commercially available. 
     Proteomics 
     The term “proteome” is defined as the totality of the proteins present in a sample (e.g. tissue, organism, or cell culture) at a certain point of time. Proteomics includes, among other things, study of the global changes of protein expression in a sample (also referred to as “expression proteomics”). Proteomics typically includes the following steps: (1) separation of individual proteins in a sample by 2-D gel electrophoresis (2-D PAGE); (2) identification of the individual proteins recovered from the gel, e.g. my mass spectrometry or N-terminal sequencing, and (3) analysis of the data using bioinformatics. 
     General Description of the mRNA Isolation, Purification and Amplification 
     The steps of a representative protocol for profiling gene expression using fixed, paraffin-embedded tissues as the RNA source, including mRNA isolation, purification, primer extension and amplification are provided in various published journal articles. (See, e.g., T. E. Godfrey et al.,  J. Molec. Diagnostics  2: 84-91 (2000); K. Specht et al.,  Am. J. Pathol.  158: 419-29 (2001), M. Cronin, et al.,  Am J Pathol  164:35-42 (2004)). Briefly, a representative process starts with cutting a tissue sample section (e.g. about 10 μm thick sections of a paraffin-embedded tumor tissue sample). The RNA is then extracted, and protein and DNA are removed. After analysis of the RNA concentration, RNA repair is performed if desired. The sample can then be subjected to analysis, e.g., by reverse transcription using gene specific promoters followed by PCR. 
     Coexpression Analysis 
     The present invention provides genes that co-express with particular response indicator genes that have been identified as having a correlation with a positive response to a platinum-based chemotherapy drug. To perform particular biological processes, genes often work together in a concerted way, i.e. they are co-expressed. Co-expressed gene groups identified for a disease process like cancer can also serve as response indicator genes. Such co-expressed genes can be assayed in lieu of, or in addition to, assaying of the response indicator gene with which they co-express. 
     One skilled in the art will recognize that many co-expression analysis methods now known or later developed will fall within the scope and spirit of the present invention. These methods may incorporate, for example, correlation coefficients, co-expression network analysis, clique analysis, etc., and may be based on expression data from RT-PCR, microarrays, sequencing, and other similar technologies. For example, gene expression clusters can be identified using pair-wise analysis of correlation based on Pearson or Spearman correlation coefficients. (See e.g, Pearson K. and Lee A.,  Biometrika  2:357 (1902); C. Spearman,  Amer. J. Psychol.  15:72-101 (1904); J. Myers, A. Well,  Research Design and Statistical Analysis , p. 508 (2 nd  Ed., 2003).) In general, a correlation coefficient of equal to or greater than 0.3 is considered to be statistically significant in a sample size of at least 20. (See e.g., G. Norman, D. Streiner,  Biostatistics: The Bare Essentials,  137-138 (3 rd  Ed. 2007).) 
     Reference Normalization 
     In order to minimize expression measurement variations due to non-biological variations in samples, e.g., the amount and quality of expression product to be measured, raw expression level data measured for a gene product (e.g., cycle threshold (Ct) measurements obtained by qRT-PCR) may be normalized relative to the mean expression level data obtained for one or more reference genes. Examples of reference genes include housekeeping genes, such as GAPDH. Alternatively, all of the assayed genes or a large subset thereof may also concurrently serve as reference genes and normalization can be based on the mean or median signal (Ct) of all of the assayed genes or a subset thereof (often referred to as “global normalization” approach). On a gene-by-gene basis, measured normalized amount of a patient tumor mRNA may be compared to the amount found in a cancer tissue reference set. See e.g., Cronin, M. et al.,  Am. Soc. Investigative Pathology  164:35-42 (2004). The normalization may be carried out such that a one unit increase in normalized expression level of a gene product generally reflects a 2-fold increase in quantity of expression product present in the sample. For further information on normalization techniques applicable to qRT-PCR data from tumor tissue, see e.g., Silva, S. et al. (2006)  BMC Cancer  6, 200; deKok, J. et al. (2005)  Laboratory Investigation  85, 154-159. 
     Kits of the Invention 
     The materials for use in the methods of the present invention are suited for preparation of kits produced in accordance with well known procedures. The present invention thus provides kits comprising agents, which may include gene-specific or gene-selective probes and/or primers, for quantitating the expression of the disclosed genes for predicting prognostic outcome or response to treatment. Such kits may optionally contain reagents for the extraction of RNA from tumor samples, in particular, fixed paraffin-embedded tissue samples and/or reagents for RNA amplification. In addition, the kits may optionally comprise the reagent(s) with an identifying description or label or instructions relating to their use in the methods of the present invention. The kits may comprise containers (including microliter plates suitable for use in an automated implementation of the method), each with one or more of the various reagents (typically in concentrated form) utilized in the methods, including, for example, pre-fabricated microarrays, buffers, the appropriate nucleotide triphosphates (e.g., dATP, dCTP, dGTP and dTTP; or rATP, rCTP, rGTP and UTP), reverse transcriptase, DNA polymerase, RNA polymerase, and one or more probes and primers of the present invention (e.g., appropriate length poly(T) or random primers linked to a promoter reactive with the RNA polymerase). Mathematical algorithms used to estimate or quantify prognostic or predictive information are also properly potential components of kits. 
     Reports 
     The methods of this invention are suited for the preparation of reports summarizing the predictions resulting from the methods of the present invention. A “report” as described herein, is an electronic or tangible document that includes elements that provide information of interest relating to a likelihood assessment and its results. A subject report includes at least a likelihood assessment, e.g., an indication as to the likelihood that a cancer patient will exhibit a positive response to a treatment regimen with a platinum-based chemotherapy drug. A subject report can be completely or partially electronically generated, e.g., presented on an electronic display (e.g., computer monitor). A report can further include one or more of: 1) information regarding the testing facility; 2) service provider information; 3) patient data; 4) sample data; 5) an interpretive report, which can include various information including: a) indication; b) test data, where test data can include a normalized level of one or more genes of interest, and 6) other features. 
     The present invention therefore provides methods of creating reports and the reports resulting therefrom. The report may include a summary of the expression levels of the RNA transcripts, or the expression products of such RNA transcripts, for certain genes in the cells obtained from the patient&#39;s tumor tissue. The report may include a prediction that the patient has an increased likelihood of a positive response to treatment with a particular chemotherapy or the report may include a prediction that the subject has a decreased likelihood of a positive response to the chemotherapy. The report may include a recommendation for a treatment modality such as surgery alone or surgery in combination with chemotherapy. The report may be presented in electronic format or on paper. 
     Thus, in some embodiments, the methods of the present invention further include generating a report that includes information regarding the patient&#39;s likelihood of a positive response to chemotherapy, particularly a treatment with a platinum-based chemotherapy drug, such as oxaliplatin. For example, the methods of the present invention can further include a step of generating or outputting a report providing the results of a patient response likelihood assessment, which can be provided in the form of an electronic medium (e.g., an electronic display on a computer monitor), or in the form of a tangible medium (e.g., a report printed on paper or other tangible medium). 
     A report that includes information regarding the likelihood that a patient will exhibit a positive response to treatment with a platinum-based chemotherapy drug, such as oxaliplatin, is provided to a user. An assessment as to the likelihood that a cancer patient will respond to treatment•with a platinum-based chemotherapy drug, such as oxaliplatin, is referred to as a “response likelihood assessment” or “likelihood assessment.” A person or entity who prepares a report (“report generator”) may also perform the likelihood assessment. The report generator may also perform one or more of sample gathering, sample processing, and data generation, e.g., the report generator may also perform one or more of: a) sample gathering; b) sample processing; c) measuring a level of a response indicator gene expression product(s); d) measuring a level of a reference gene product(s); and e) determining a normalized level of a response indicator gene expression product(s). Alternatively, an entity other than the report generator can perform one or more sample gathering, sample processing, and data generation. 
     The term “user” or “client” refers to a person or entity to whom a report is transmitted, and may be the same person or entity who does one or more of the following: a) collects a sample; b) processes a sample; c) provides a sample or a processed sample; and d) generates data (e.g., level of a predictive gene expression product(s); level of a reference gene product(s); normalized level of a predictive gene expression product(s)) for use in the likelihood assessment. In some cases, the person or entity who provides sample collection and/or sample processing and/or data generation, and the person who receives the results and/or report may be different persons, but are both referred to as “users” or “clients.” In certain embodiments, e.g., where the methods are completely executed on a single computer, the user or client provides for data input and review of data output. A “user” can be a health professional (e.g., a clinician, a laboratory technician, a physician (e.g., an oncologist, surgeon, pathologist), etc.). 
     In embodiments where the user only executes a portion of the method, the individual who, after computerized data processing according to the methods of the invention, reviews data output (e.g., results prior to release to provide a complete report, a complete, or reviews an “incomplete” report and provides for manual intervention and completion of an interpretive report) is referred to herein as a “reviewer.” The reviewer may be located at a location remote to the user (e.g., at a service provided separate from a healthcare facility where a user may be located). 
     Where government regulations or other restrictions apply (e.g., requirements by health, malpractice, or liability insurance), all results, whether generated wholly or partially electronically, are subjected to a quality control routine prior to release to the user. 
     Computer-Based Systems and Methods 
     The methods and systems described herein can be implemented in numerous ways. In one embodiment of the invention, the methods involve use of a communications infrastructure, for example, the internet. Several embodiments of the invention are discussed below. The present invention may also be implemented in various forms of hardware, software, firmware, processors, or a combination thereof. The methods and systems described herein can be implemented as a combination of hardware and software. The software can be implemented as an application program tangibly embodied on a program storage device, or different portions of the software implemented in the user&#39;s computing environment (e.g., as an applet) and on the reviewer&#39;s computing environment, where the reviewer may be located at a remote site (e.g., at a service provider&#39;s facility). 
     In an embodiment of the invention, during or after data input by the user, portions of the data processing can be performed in the user-side computing environment. For example, the user-side computing environment can be programmed to provide for defined test codes to denote a likelihood “score,” where the score is transmitted as processed or partially processed responses to the reviewer&#39;s computing environment in the form of test code for subsequent execution of one or more algorithms to provide a result and/or generate a report in the reviewer&#39;s computing environment. The score can be a numerical score (representative of a numerical value) or a non-numerical score representative of a numerical value or range of numerical values (e.g., “A”: representative of a 90-95% likelihood of a positive response; “High”: representative of a greater than 50% chance of a positive response (or some other selected threshold of likelihood); “Low”: representative of a less than 50% chance of a positive response (or some other selected threshold of likelihood), and the like. 
     As a computer system, the system generally includes a processor unit. The processor unit operates to receive information, which can include test data (e.g., level of a predictive gene product(s); level of a reference gene product(s); normalized level of a predictive gene product(s); and may also include other data such as patient data. This information received can be stored at least temporarily in a database, and data analyzed to generate a report as described above. 
     Part or all of the input and output data can also be sent electronically. Certain output data (e.g., reports) can be sent electronically or telephonically (e.g., by facsimile, using devices such as fax back). Exemplary output receiving devices can include a display element, a printer, a facsimile device and the like. Electronic forms of transmission and/or display can include email, interactive television, and the like. In an embodiment of the invention, all or a portion of the input data and/or output data (e.g., usually at least the final report) are maintained on a web server for access, preferably confidential access, with typical browsers. The data may be accessed or sent to health professionals as desired. The input and output data, including all or a portion of the final report, can be used to populate a patient&#39;s medical record that may exist in a confidential database as the healthcare facility. 
     The present invention also contemplates a computer-readable storage medium (e.g., CD-ROM, memory key, flash memory card, diskette, etc.) having stored thereon a program which, when executed in a computing environment, provides for implementation of algorithms to carry out all or a portion of the results of a response likelihood assessment as described herein. Where the computer-readable medium contains a complete program for carrying out the methods described herein, the program includes program instructions for collecting, analyzing and generating output, and generally includes computer readable code devices for interacting with a user as described herein, processing that data in conjunction with analytical information, and generating unique printed or electronic media for that user. 
     Where the storage medium includes a program that provides for implementation of a portion of the methods described herein (e.g., the user-side aspect of the methods (e.g., data input, report receipt capabilities, etc.)), the program provides for transmission of data input by the user (e.g., via the interne, via an intranet, etc.) to a computing environment at a remote site. Processing or completion of processing of the data is carried out at the remote site to generate a report. After review of the report, and completion of any needed manual intervention, to provide a complete report, the complete report is then transmitted back to the user as an electronic document or printed document (e.g., fax or mailed paper report). The storage medium containing a program according to the invention can be packaged with instructions (e.g., for program installation, use, etc.) recorded on a suitable substrate or a web address where such instructions may be obtained. The computer-readable storage medium can also be provided in combination with one or more reagents for carrying out a response likelihood assessment (e.g., primers, probes, arrays, or such other kit components). 
     Having described the invention, the same will be more readily understood through reference to the following Examples, which are provided by way of illustration, and are not intended to limit the invention in any way. All citations through the disclosure are hereby expressly incorporated by reference. 
     EXAMPLES 
     Example 1 
     In this study, a synthetic-lethal small interfering RNA (siRNA) screen was performed on human CRC cells to identify genes whose loss-of-function (LOF) modulates tumor cell response to oxaliplatin. The screen targeted 500 genes involved in DNA repair, drug transport, metabolism, apoptosis, and regulation of the cell cycle (Table 1). Four unique siRNA duplexes were used over seven different oxaliplatin concentrations per gene. By this method, 82 genes were shown to modify the response to oxaliplatin (Table 2). Of these, 27 genes were chosen for further study whose loss of expression significantly altered the response to oxaliplatin, by either increased sensitivity or increased resistance (Table 3). 
     Cell Lines and Antibodies 
     Colon cancer cell lines HCT116 (ATCC# CCL-247) and SW480 (ATCC# CCL-228) were obtained from the American Type Culture Collection (Manassas, Va.), and were maintained in McCoy&#39;s 5A media supplemented with 10% fetal bovine serum, 1.5 mM L-glutamine, and 1% Antibiotic-Antimycotic (Invitrogen, Carlsbad, Calif.). 
     siRNA Screening and Drug Treatments 
     Four siRNA sequences were selected for each targeted gene from the Whole Human Genome V1.00 and Druggable Genome V2.0® siRNA libraries (Qiagen, Valencia; CA) to create six (6) custom 384-well assay plates. All assay plates included negative control siRNAs (Non-Silencing, All-Star Non-Silencing, and GFP, all from Qiagen), and two positive control siRNAs (UBBs1 and All-Star Cell Death Control® from Qiagen). Selected siRNAs were printed individually into white solid 384-well plates (1 μl of 0.667 μM siRNA per well for a total of 9 ng siRNA) using a Biomek FX® (Beckman Coulter, Brea, Calif.). Lipofectamine 2000® (Invitrogen, Carlsbad, Calif.) was diluted in serum-free McCoy&#39;s 5A media and 20 μl was transferred into each well of the 384-well plate containing siRNAs (final ratio of 7.4n1 lipid per ng siRNA). After an incubation period of 30 minutes at room temperature to allow the siRNA and lipid to form complexes, 20 μl of HCT 116 cells (2.5×10 4  cells/ml) in antibiotic-free McCoy&#39;s 5A media were added into each well. Transfected cells were incubated for 24 hours prior to the addition of 10 μl per well of different concentrations of oxaliplatin (35.0, 3.75, 3.0, 2.0, and 1.5 μM) and vehicle control (DMSO) for a total assay volume of 50 μl. Oxaliplatin was obtained from Sigma (St. Louis, Mo.). Cell viability was measured 72 h post drug treatment using the CellTiter-Glo® assay (Promega, Madison, Wis.), measured on an Analyst GT Multimode reader (Molecular Devices, Sunnyvale, Calif.). A repliCate of the screen was also performed, resulting in a total of 56 data points per gene. Cell viability data was normalized to the median value of All-Star NS negative control siRNA and IC 50  values were calculated using Prism 5.0® (GraphPad, La Jolla, Calif.). 
     Statistical Analysis 
     The effect of siRNA treatment on the IC 50  of oxaliplatin was expressed as the log 2  fold-shift of the median IC 50  of siRNA-treated cells relative to the median IC 50  of non-silencing siRNA control-treated cells. Hits were identified as those with a median IC 50  shift greater than the median IC 50 +3 median absolute deviation (median±3MAD) (Chung, N., et al., Median absolute deviation to improve hit selection for genome-scale RNAi screens.  J Biomol Screen,  2008. 13(2): p. 149-58; Birmingham, A., et al., Statistical methods for analysis of high-throughput RNA interference screens.  Nat Methods,  2009. 6(8): p. 569-75). 
     To assign statistical significance to siRNA hits identified from the siRNA screen, collective activities of the 4 individual siRNAs used for each gene were modeled using the redundant siRNA activity (RSA) analysis. Briefly, the normalized, log 2  transformed IC 50  shifts of each siRNA were rank ordered. Subsequently, the rank distribution of all siRNAs targeting the same gene was examined and a P value was calculated based on an iterative hypergeometric distribution formula (Konig, R., et al., A probability-based approach for the analysis of large-scale RNAi screens.  Nat Methods,  2007. 4(10): p. 847-9). siRNAs with P-values&lt;0.05 were considered as significant. Subsequently, only genes with a median IC 50  shift&gt;median IC 50 ±3 MAD and an RSA P value&lt;0.05 were considered robust hits and analyzed further. All other tests of significance were two-sided, and P values&lt;0.05 were considered significant. 
     Results 
     A custom siRNA library targeting 500 genes with putative roles in DNA damage repair, apoptosis, regulation of the cell cycle, drug metabolism and transport, was screened using the colorectal cancer tumor cell line, HCT 116 (Table 1). The siRNA library contained four siRNAs targeting each of the 500 genes, with each siRNA transfected individually. The screen was performed in duplicate, with a non-silencing siRNA negative control. siRNAs were used at 17 nM to reduce off-target effects. Twenty-four hours after transfection, 5 different concentrations of oxaliplatin (35.0, 3.75, 3.0, 2.0, and 1.5 μM) and vehicle control (DMSO) were added and cell viability was measured 72 hours after addition of drug. The deviation between the replicates in the siRNA screen is shown in  FIG. 1A  by plotting the log 2  fold shift IC 50  of the first replicate against the log 2  fold shift IC 50  of the second replicate. The R 2  value was 0.60, as indicated. Moreover, the mean Z′ factor for the screen was 0.67, suggesting that that assay had a robust signal-to-noise ratio ( FIG. 1B ). 
     Two criteria were used to limit the discovery of false positives. First, all genes whose silencing shifted the IC 50  of oxaliplatin≧±3 median absolute deviations from the median IC 50  of oxaliplatin in control cells were identified. This approach (median±k MAD) has been shown to be robust to outliers and effective in controlling the false positive rate in siRNA screens (Chung, N., et al., Median absolute deviation to improve hit selection for genome-scale RNAi screens.  J Biomol Screen,  2008. 13(2): p. 149-58; Birmingham, A., et al., Statistical methods for analysis of high-throughput RNA interference screens.  Nat Methods,  2009. 6(8): p. 569-75). Second, the collective activities of the 4 individual siRNAs used for each gene were modelled using the redundant siRNA activity (RSA) analysis (Konig, R., et al., A probability-based approach for the analysis of large-scale RNAi screens. Nat Methods, 2007. 4(10): p. 847-9). siRNAs with P-values&lt;0.05 were considered significant (Table 2). 27 genes that satisfied both these criteria were identified ( FIG. 2A ; Table 3) and analyzed further. 
     To survey the biological pathways and processes represented by these twenty-seven genes, the PANTHER® database was utilized (Thomas, P. D., et al., PANTHER: a browsable database of gene products organized by biological function, using curated protein family and subfamily classification.  Nucleic Acids Res,  2003. 31(1): p. 334-41). The predominant biological process of identified genes is DNA repair and DNA metabolism, as well as nucleoside, nucleotide, and nucleic acid metabolism ( FIG. 2B ). Additionally, to determine if any of the hits were enriched for known biological processes or canonical pathways in a statistically significant manner, the 27 genes were categorized using Gene Ontology® (GOTermFinder®) (Boyle, E. I., et al., GO::TermFinder—open source software for accessing Gene Ontology information and finding significantly enriched Gene Ontology terms associated with a list of genes.  Bioinformatics,  2004. 20(18): p. 3710-5) ( FIG. 3A ), and Ingenuity® Pathway Analysis (www.ingenuity.com) ( FIG. 3B ). This analysis also revealed that many of these genes functioned in DNA metabolism, response to DNA damage, cell cycle, and apoptosis. It is noteworthy that there was no significant association with drug metabolism, drug transport, or generalized resistance to chemotherapies amongst these gene hits. 
     Example 2 
     Twelve out of the 27 genes from Example 1 were selected for validation using additional siRNAs. These genes (BRIP1, CDKN1A, CUL4B, LTBR, MBD4, MCM3, NHEJ1, PRDX4, PTTG1, SFHM1, TMEM30A, and TP53) were selected based on the significance analysis and/or functional categorization. 
     For validation of siRNA hits, ON-TARGETplus® siRNAs (Thermo Scientific, Waltham Mass.), containing pools of 4 siRNAs per gene, were utilized (Table 4). 70 μl of HCT 116 or SW480 cells (1.0×10 5  cells/ml) were plated in black, clear-bottomed 96-well plates in antibiotic-free McCoy&#39;s 5A medium and allowed to adhere overnight. Cells were then transfected with 25 nM siRNA using DharmaFECT® transfection reagent (Thermo Scientific, Waltham, Mass.). Following a 4 hr incubation, 10 μl per well of an 11-point, 2-fold serial dilution of oxaliplatin (50 μM maximum) was then added, for a total assay volume of 100 μl. Assays were performed in triplicate, with ON-TARGETplus Non-Targeting siRNA® (Thermo Scientific, Waltham, Mass.) as a negative control, with biological replicates. Cell viability was measured 72 h later using the CellTiter 96® AQueous One Solution Cell Proliferation Assay (Promega, Madison, Wis.), and IC 50  values calculated using Prism 5.0® (GraphPad, La Jolla, Calif.). siRNA knockdown was validated by qRT-PCR using the High-Capacity cDNA Reverse Transcription Kite (Life Technologies, Carlsbad, Calif.) and qPCR using the 7900 HT Fast Real-Time PCR System® (Life Technologies, Carlsbad, Calif.) with gene-specific primers (ABI, Carlsbad, Calif.). ( FIG. 4A ). 
     The retested genes were considered to be validated if the resulting IC 50  of oxaliplatin shifted &gt;50% from the IC 50  of oxaliplatin in cells treated with non-silencing siRNAs. All twelve of the genes selected for validation exceeded this 50% threshold ( FIG. 5A ). 
     Nine of these genes (CUL4B, LTBR, MBD4, MCM3, NHEJ1, PRDX4, PTTG1, SFHM1, and TMEM30A) were then examined in the oxaliplatin-resistant SW480 colorectal tumor cell line (Rixe, O., et al., Oxaliplatin, tetraplatin, cisplatin, and carboplatin: spectrum of activity in drug-resistant cell lines and in the cell lines of the National Cancer Institute&#39;s Anticancer Drug Screen panel.  Biochem Pharmacol,  1996. 52(12): p. 1855-65). Silencing of each of these 9 genes, all of which conferred increased sensitivity to the HCT 116 tumor cell line, also increased sensitivity of the SW480 tumor cell line to oxaliplatin ( FIG. 5B ). 
     Example 3 
     To independently test whether the expression of the identified genes relates to tumor cell sensitivity to oxaliplatin, the effects of overexpression of two genes, LTBR and TMEM30A, on response to oxaliplatin were assayed. 
     Full-length LTBR and TMEM30A open reading frames were cloned into pCMV-XL4 (Origene, Rockville, Md.) and validated by sequencing. Transfection was performed using Turbofectin 8.0® (Origene, Rockville, Md.) in a 96-well format as per manufacturer&#39;s instructions using 100 ng cDNA per well. Following a 4 hr incubation, 10 μl per well of an 11-point, 2-fold serial dilution of oxaliplatin (50 μM maximum) was then added. Assays were performed in triplicate, using the empty pCMV-XL4 vector as negative control, with biological replicates. Cell viability was measured 72 h later using the CellTiter 96® AQueous One Solution Cell Proliferation Assay (Promega, Madison, Wis.), and IC 50  values calculated using Prism 5.0® (GraphPad, La Jolla, Calif.). Overexpression of cDNA was validated by qRT-PCR using the High-Capacity cDNA Reverse Transcription Kit® (Life Technologies, Carlsbad, Calif.) and qPCR using the 7900 HT Fast Real-Time PCR System® (Life Technologies, Carlsbad, Calif.) with gene-specific primers (ABI, Carlsbad, Calif.). 
     Transient overexpression of full-length LTBR or TMEM30A (validated by qPCR;  FIG. 4B ) increased the IC 50  of oxaliplatin &gt;2-fold ( FIG. 5C ), significantly increasing the resistance of the HCT 116 cell line to oxaliplatin, as predicted by the results with siRNA silencing. 
     Example 4 
     To begin to address the cellular mechanisms responsible for modulated cell sensitivity to oxaliplatin, it was asked if siRNA silencing of the identified genes altered the amount of DNA damage acquired by tumor cells treated with oxaliplatin. DNA damage was assessed by quantification of apurinic/apyrimidinic (AP) sites (BioVision, Mountain View, Calif.) following manufacturer&#39;s instruction. 
     Platinum-DNA adducts formed upon exposure to platinum-based chemotherapies are thought to be primarily removed through the nucleotide excision repair pathway (NER). Using the in vitro assay that measures the number of apurinic/apyrimidinic sites on the DNA of oxaliplatin-treated cells, it was found that siRNA-silencing of CUL4B and NHEJ1, both with known roles in the repair of DNA damage via the NER (Guerrero-Santoro, J., et al., The cullin 4B-based UV-damaged DNA-binding protein ligase binds to UV-damaged chromatin and ubiquitinates histone H2A.  Cancer Res,  2008. 68(13): p. 5014-22; Valencia, M., et al., NEJ1 controls non-homologous end joining in  Saccharomyces cerevisiae. Nature,  2001. 414(6864): p. 666-9) significantly increased the amount of DNA damage relative to oxaliplatin-treated control cells ( FIG. 6A ). siRNA silencing of two other genes with known roles in DNA replication and repair, MBD4 and MCM3 (Riccio, A., et al., The DNA repair gene MBD4 (MEDI) is mutated in human carcinomas with microsatellite instability.  Nat Genet,  1999. 23(3): p. 266-8; Madine, M. A., et al., MCM3 complex required for cell cycle regulation of DNA replication in vertebrate cells.  Nature,  1995. 375(6530): p. 421-4) also increased the amount of DNA damage accumulated upon treatment with oxaliplatin ( FIG. 6A ), although the increase did not reach statistical significance (P&lt;0.05). 
     Second, alterations in the phosphorylation of signaling nodes of several pathways whose activity may contribute significantly to changes in cell proliferation were studied, including the mitogen-activated protein kinase cascade, JAK/STAT, and NFκB pathways. To this end, phosphorylation status of AKT1 (Ser437), MEK1 (Ser217/222), p38 MAPK (Thr180/Tyr182), STAT3 (Tyr705), and NFκB p65 (Ser536), was determined using the PathScan Signaling Nodes Multi-Target Sandwich ELISA® (Cell Signaling Technology, Danvers, Mass.) as per manufacturer&#39;s instructions. In addition, the phosphorylation status of p53 (Ser15), Bad (Ser112), PARP (Asp214), and cleavage status of Caspase-3 were determined using the PathScan Apoptosis Multi-Target Sandwich ELISA® (Cell Signaling Technology, Danvers, Mass.) following manufacturer&#39;s instructions. Raw signal intensity was normalized to either total Akt or Bad protein levels. Assays were performed in duplicate, and the log 2  fold-change (OD 450  siRNA-treated cells/OD 450  non-silencing siRNA-treated cells), following median normalization, was converted into a heatmap using Java TreeView. 
     Quantitative analyses to determine the activity of p-Akt1, p-Mek1, p-p38 MAPK, p-Stat3, and p-NFκB p65 were performed. Hierarchical clustering of phosphorylation levels (relative to control cells) revealed diverse and non-overlapping clusters of pathway signaling following siRNA silencing of the 12 selected genes of Example 2, with the noticeable exception of pNFκB p65, suggesting that distinct cellular mechanisms for each gene are likely responsible for altered cell survival ( FIG. 6B ). Similarly, when the activities of several gene regulators of apoptosis were probed, including p-p53, p-Bad, cleaved caspase 3 and cleaved PARP, distinct clusters of pathway activity were observed, suggesting that upon siRNA silencing of the genes, both caspase-dependent and caspase-independent pathways regulating changes in apoptosis and/or cell death are modulated in response to DNA damage upon treatment with oxaliplatin ( FIG. 6C ). 
     Example 5 
     The effects that siRNA silencing of the 12 genes of Example 2 would have on cell cycle were also evaluated. 
     Transfections were performed as described in Example 2, using six-well plates (5×10 5  cells/well). Cells were collected by gentle trypsinization, followed by centrifugation at 500 rpm for 5 min, fixed with 70% ethanol at −20° C., washed with PBS, and re-suspended in 0.5 ml of PBS containing propidium iodide (10 μg/ml). After a final incubation at 37° C. for 30 min with RNase A (Sigma, St. Louis, Mo.), cells were analyzed by flow cytometry using a LSR II flow cytometer (Becton Dickinson, Franklin Lakes, N. J.) at ˜200 events/sec using the DNA QC Particles Kit® following manufacturer&#39;s instructions (Becton. Dickinson, Franklin Lakes, N. J.). Data were analyzed using FlowJo software (Tree Star, Ashland, Oreg.). 
     Cell cycle analysis indicates that upon treatment with oxaliplatin, all siRNA-treated cells, including those with increased siRNA-mediated resistance to oxaliplatin (CDKN1A and p53), exhibited a significant decrease in the percentage of cells in G1 with a concomitant increase in the percentage of cells in G2/M as compared to control cells ( FIG. 7 ). This is consistent with previous observations that G2/M arrest facilitates platinum-mediated cell death (Sorenson, C. M. and A. Eastman, “Influence of cis-diamminedichloroplatinum(II) on DNA Synthesis sand Cell Cycle Progression in Excision Repair Proficient and Deficient Chinese Hamster Ovary Cells,”  Cancer Res.,  1988. 48(23): p. 6703-7; Sorenson, C. M. and A. Eastman, “Mechanism of cis-diamminedichloroplatinum(II)-Induced Cytotoxicity: Role of G2 Arrest and DNA Double-Strand Breaks,”  Cancer Res.,  1988. 48(16): p. 4484-8), although it is of note that there were no gross differences between oxaliplatin-sensitive and -resistant cells. 
     Example 6 
     To further understand the functional relationships between those genes whose loss of expression altered the sensitivity of tumor cells to oxaliplatin, an extensive bioinformatic analysis was performed using the statistically significant genes validated in the initial screen to identify relevant networks of interacting proteins. 
     Data were analyzed through the use of Ingenuity® Pathways Analysis (Ingenuity Systems, www.ingenuity.com), PANTHER® (www.panther.org) (Thomas, P. D., et al., PANTHER: a browsable database of gene products organized by biological function, using curated protein family and subfamily classification.  Nucleic Acids Res,  2003. 31(1): p. 334-41), or GOTermFinder® (go.princeton.edu/cgi-bin/GOTermFinder) (Boyle, E. L, et al., GO::TermFinder—open source software for accessing Gene Ontology information and finding significantly enriched Gene Ontology terms associated with a list of genes. Bioinformatics, 2004. 20(18): p. 3710-5). Briefly, the functional analysis of siRNA hits identified the biological functions that were most significantly associated with identified genes. The network-associated genes with biological functions in the Ingenuity Pathways Knowledge Base were considered for the analysis. Fischer&#39;s exact test was used to calculate the probability that each biological function assigned to that network is due to chance alone. 
     The most significantly enriched interaction network is heavily populated with genes that have roles in DNA replication, recombination, repair and cell cycle progression ( FIG. 8 ). It is, however, of interest that this interaction network contains nodes previously not associated with response to oxaliplatin, which link it to proteins from the canonical (BCL10, TRAF6) and non-canonical NFkB pathways (LTBR, TRAF3, PRDX4) (Perkins, N. D., “Integrating Cell-Signalling Pathways with NF-kappaB and IKK Function,”  Nat Rev Mol Cell Biol,  2007. 8(1): p. 49-62), as well as the estrogen signaling (ESR1, MPG, MDB2), apoptosis (BCL2, BCL2L10, BCL10, DFFA, CASP3, and BIRC2), and BRCA1/2-signaling pathways (BRCA1, BRCA2, SHFM1, and BRIP1). 
     Example 7 
     The genes listed in any of Tables 1-4, as well as any of the gene subsets identified in Examples 1 and Example 2, are studied on tissue samples obtained from human patients with colorectal cancer enrolled in the National Surgical Adjuvant Breast and Bowel Project (NSABP) protocol C-07 (NSABP C-07) phase III clinical trial. See Kuebler J. P. et al., “Oxaliplatin Combined with Weekly Bolus Fluorouracil and Leucovorin as Surgical Adjuvant Chemotherapy for Stage II and III Colon Cancer: Results from NSABP C-07,”  J. Clin. Oncol.  25:2198-2204 (2007). An objective of the study is to determine whether there is a significant relationship between the expression of the genes and clinical outcome in the patient who received oxaliplatin after colon resection surgery. Improvement in a clinical endpoint, such as recurrence-free interval (RFI), distant recurrence-free interval (DRFI), overall survival (OS), and disease-free survival (DFS), reflects an increased likelihood of response to treatment with oxaliplatin and a likelihood of a positive response. 
     Patients in the NSABP C-07 study had either stage II or stage III colorectal cancer and had undergone a potentially curative resection. Their tissue samples were archived, formalin-fixed, and paraffin-embedded prior to treatment. Patients were then randomly assigned to one of the following treatment regimens: (1) FULV: 5-fluorouracil (5-FU) 500 mg/m 2  intravenous (IV) bolus weekly for 6 weeks plus leucovorin 500 mg/m 2  IV weekly for 6 weeks during each 8-week cycle for three cycles; or (2) FLOX: the same FULV regimen with oxaliplatin 85 mg/m 2  IV administered on weeks 1, 3, and 5 of each 8-week cycle for three cycles. Data regarding the clinical responses of each patient are available. See id. 
     The expression of one or more of the 500 genes, or any gene subset, is quantitatively measured for each patient from the archived, formalin-fixed paraffin-embedded tissue (FPET) samples by RT-PCR. The primers and probes for each of the 500 genes and reference genes may be readily determined by methods known in the art. The Accession Number as given in the Entrez Gene online database by the National Center for Biotechnology Information for each gene is provided in Table 1. For normalization of extraneous effects, cycle threshold (Ct) measurements obtained by RT-PCR are normalized relative to the mean expression of a set of reference genes. 
     For each of the genes, the Cox proportional hazard model is used to examine the relationship between gene expression and recurrence-free interval (RFI). The likelihood ratio is used as a test of statistical significance. The method of Benjamini and Hochberg (Benajmini™, Y. and Hochberg, Y. (1995), Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing.  J. R. Statist. Soc. B.  57:289-300), as well as resampling and permuation based methods (Tusher, V. G. et al. (2001), Significance Analysis of Microarrays Applied to the Ionizing Radiation Response,  PNAS  98:5116-5121; Storey J. D. et al. (2001), Estimating False Discovery Rates Under Dependence, With Applications to DNA Microarrays, Stanford: Stanford University, Department of Statistics,  Technical Report  2001-28; Korn E. L. et al. (2001), Controlling the Number of False Discoveries: Application to High-Dimensional Genomic Data,  Technical Report  003, National Cancer Institute) may be applied to the resulting set of p-values to estimate false discovery rates. A gene with a p-value of &lt;0.05 is generally considered to have a significant correlation between its gene expression and a positive response to treatment. 
     A hazard ratio (HR) is calculated for each gene from the Cox proportion hazards regression model for the FLOX group. A gene with HR&gt;1 indicates higher recurrence risk after treatment and therefore, a decreased likelihood of a positive response as gene expression increases. A gene with HR&lt;1 indicates lower recurrence risk after treatment and therefore, an increased likelihood of a positive response as gene expression increases. Additionally, the hazard ratios provide an assessment of the contribution of the instantaneous risk of recurrence at time t conditional on a recurrence not occurring by time t. For an individual with gene expression measurement X, the instantaneous risk of recurrence at time t, λ(t|X) is given by the relationship λ(t|X)=λ o (t)·exp[β·X] where λ o (t) is the baseline hazard at time t and p is the log hazard ration (β=ln [HR]). Furthermore, the survivor function at time t is given by S(t|X)=S o (t) exP[β·X] , where S o (t) is the baseline survivor function at time t. Consequently, the risk of recurrence at time t for a patient with a gene expression measurement of X is given by 1−S(t|X). In this way, an individual patient&#39;s estimated risk of recurrence may be derived from an observed gene expression measurement. 
     A hazard ratio may also be calculated for each gene for the FULV group to identify genes whose expression is associated specifically with response to oxaliplatin. A test can be performed to evaluate whether the HR associated with gene expression in the FULV group (received only 5-FU and leucovorin) is sufficiently different from the HR associated with gene expression in the FLOX group (received oxaliplatin in addition to 5-FU and leucovorin). 
     Accordingly, increased expression level of the one or more genes selected from the group ATP6V0C, BCL10, BCL2L10, BFAR, BRIP1, CARD6, CCND1, CDC20, CDC25A, CFLAR, CHAF1A, CRADD, CUL4B, DFFA, E2F2, E2F4, E2F6, GADD45B, HMG20B, IL8, LTBR, MBD2, MBD3, MBD4, MCM3, MCM4, MCM6, MGST3, MPG, MRPL3, MSH4, NHEJ1, OGT, PAICS, PPP2R5C, PRDX4, PTTG1, RAD51L1, RARA, RBM4, RECQL, RRM1, SHFM1, SPO11, TMEM30A, UBE2A, UBE2S, XAB2, and XRCC2 is negatively correlated with a likelihood that a patient with colorectal cancer will exhibit a positive response to treatment comprising oxaliplatin, and increased expression level of one or more genes selected from ABL1, APAF1, BAX, CARD4, CASP5, CCT5, CDKN1A, CDKN3, CIDEA, CRIP2, CUL1, CYP1A2, DNMT1, ERCC4, FANCE, GSTT1, GSTZ1, GTF2H5, KPNA2, MRPS12, MSH5, NFKB1, PTEN, SMARCA4, SND1, SOX4, SUMO1, TARS, TNFRSF10A, TNFSF8, TP53, XPC, and XRCC3 is positively correlated with a likelihood that a patient with colorectal cancer will exhibit a positive response to treatment comprising oxaliplatin. 
     While the present invention has been described with reference to the specific embodiments thereof, it should be understood by those skilled in the art that various changes may be made and equivalents may be substituted without departing from the true spirit and scope of the invention. In addition, many modifications may be made to adapt a particular situation, material, composition of matter, process, process step or steps, to the objective, spirit and scope of the present invention. All such modifications are intended to be within the scope of the claims appended hereto. 
     Table 1 
       
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 1 
               
               
                   
               
               
                 Symbol 
                 Entrez ID 
                 GeneBank 
                 Description 
                 Exemplary Pathway 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 BAG4 
                 9530 
                 NM_004874 
                 BCL2-associated athanogene 4 
                 Apoptosis 
               
               
                 BAK1 
                 578 
                 NM_001188 
                 BCL2-antagonist/killer 1 
                 Apoptosis 
               
               
                 BAX 
                 581 
                 NM_004324 
                 BCL2-associated X protein 
                 Drug Resistance 
               
               
                 BCCIP 
                 56647 
                 NM_016567 
                 BRCA2 and CDKN1A interacting protein 
                 Cell Cycle 
               
               
                 BCL10 
                 8915 
                 NM_003921 
                 B-cell CLL/lymphoma 10 
                 Apoptosis 
               
               
                 BCL2 
                 596 
                 NM_000633 
                 B-cell CLL/lymphoma 2 
                 Drug Resistance 
               
               
                 BCL2A1 
                 597 
                 NM_004049 
                 BCL2-related protein A1 
                 Apoptosis 
               
               
                 BCL2L1 
                 598 
                 NM_138578 
                 BCL2-like 1 
                 Apoptosis 
               
               
                 BCL2L10 
                 10017 
                 NM_020396 
                 BCL2-like 10 (apoptosis facilitator) 
                 Apoptosis 
               
               
                 BCL2L11 
                 10018 
                 NM_006538 
                 BCL2-like 11 (apoptosis facilitator) 
                 Apoptosis 
               
               
                 BCL2L2 
                 599 
                 NM_004050 
                 BCL2-like 2 
                 Apoptosis 
               
               
                 BCLAF1 
                 9774 
                 NM_014739 
                 BCL2-associated transcription factor 1 
                 Apoptosis 
               
               
                 BFAR 
                 51283 
                 NM_016561 
                 Bifunctional apoptosis regulator 
                 Apoptosis 
               
               
                 BGN 
                 633 
                 BC004244 
                 Biglycan 
                 Colon ODX 
               
               
                 BID 
                 637 
                 NM_001196 
                 BH3 interacting domain death agonist 
                 Apoptosis 
               
               
                 BIK 
                 638 
                 NM_001197 
                 BCL2-interacting killer (apoptosis-inducing) 
                 Apoptosis 
               
               
                 BIRC2 
                 329 
                 NM_001166 
                 Baculoviral IAP repeat-containing 2 
                 Apoptosis 
               
               
                 BIRC3 
                 330 
                 NM_001165 
                 Baculoviral IAP repeat-containing 3 
                 Apoptosis 
               
               
                 BIRC5 
                 332 
                 NM_001168 
                 Baculoviral IAP repeat-containing 5 (survivin) 
                 p53 Pathway 
               
               
                 BIRC6 
                 57448 
                 NM_016252 
                 Baculoviral IAP repeat-containing 6 (apollon) 
                 Apoptosis 
               
               
                 BIRC8 
                 112401 
                 NM_033341 
                 Baculoviral IAP repeat-containing 8 
                 Apoptosis 
               
               
                 BLM 
                 641 
                 NM_000057 
                 Bloom syndrome 
                 DNA Damage Repair 
               
               
                 BLMH 
                 642 
                 NM_000386 
                 Bleomycin hydrolase 
                 Drug Resistance 
               
               
                 BNIP1 
                 662 
                 NM_001205 
                 BCL2/adenovirus E1B 19kDa interacting protein 1 
                 Apoptosis 
               
               
                 BNIP2 
                 663 
                 NM_004330 
                 BCL2/adenovirus E1B 19kDa interacting protein 2 
                 Apoptosis 
               
               
                 BNIP3 
                 664 
                 NM_004052 
                 BCL2/adenovirus E1B 19kDa interacting protein 3 
                 Apoptosis 
               
               
                 BNIP3L 
                 665 
                 NM_004331 
                 BCL2/adenovirus E1B 19kDa interacting protein 3-like 
                 Apoptosis 
               
               
                 BRAF 
                 673 
                 NM_004333 
                 V-raf murine sarcoma viral oncogene homolog B1 
                 Apoptosis 
               
               
                 BRCA1 
                 672 
                 NM_007294 
                 Breast cancer 1, early onset 
                 p53 Pathway 
               
               
                 BRCA2 
                 675 
                 NM_000059 
                 Breast cancer 2, early onset 
                 p53 Pathway 
               
               
                 BRIP1 
                 83990 
                 AF360549 
                 BRCA1 interacting protein C-terminal helicase 1 
                 DNA Damage Repair 
               
               
                 BTG2 
                 7832 
                 NM_006763 
                 BTG family, member 2 
                 p53 Pathway 
               
               
                 C13orf15 
                 28984 
                 NM_014059 
                 Chromosome 13 open reading frame 15 
                 Cell Cycle 
               
               
                 C18orf37 
                 125476 
                 NM_001098817 
                 chromosome 18 open reading frame 37 
                 DNA Damage Repair 
               
               
                 CANX 
                 821 
                 NM_001746 
                 calnexin 
                 DNA Damage Repair 
               
               
                 CARD6 
                 84674 
                 NM_032587 
                 Caspase recruitment domain family, member 6 
                 Apoptosis 
               
               
                 CARD8 
                 22900 
                 NM_014959 
                 Caspase recruitment domain family, member 8 
                 Apoptosis 
               
               
                 CARM1 
                 10498 
                 NM_199141 
                 coactivator-associated arginine methyltransferase 1 
                 DNA Damage Repair 
               
               
                 CASP1 
                 834 
                 NM_033292 
                 Caspase 1, apoptosis-related cysteine peptidase 
                 Apoptosis 
               
               
                   
                   
                   
                 (interleukin 1, beta, convertase) 
               
               
                 CASP10 
                 843 
                 NM_001230 
                 Caspase 10, apoptosis-related cysteine peptidase 
                 Apoptosis 
               
               
                 CASP14 
                 23581 
                 NM_012114 
                 Caspase 14, apoptosis-related cysteine peptidase 
                 Apoptosis 
               
               
                 CASP2 
                 835 
                 NM_032982 
                 Caspase 2, apoptosis-related cysteine peptidase 
                 Apoptosis 
               
               
                   
                   
                   
                 (neural precursor cell expressed, developmentally 
               
               
                   
                   
                   
                 down-regulated 2) 
               
               
                 CASP3 
                 836 
                 NM_004346 
                 Caspase 3, apoptosis-related cysteine peptidase 
                 Apoptosis 
               
               
                 CASP4 
                 837 
                 NM_001225 
                 Caspase 4, apoptosis-related cysteine peptidase 
                 Apoptosis 
               
               
                 CASP5 
                 838 
                 NM_004347 
                 Caspase 5, apoptosis-related cysteine peptidase 
                 Apoptosis 
               
               
                 CASP6 
                 839 
                 NM_032992 
                 Caspase 6, apoptosis-related cysteine peptidase 
                 Apoptosis 
               
               
                 CASP7 
                 840 
                 NM_001227 
                 Caspase 7, apoptosis-related cysteine peptidase 
                 Apoptosis 
               
               
                 CASP8 
                 841 
                 NM_001228 
                 Caspase 8, apoptosis-related cysteine peptidase 
                 Apoptosis 
               
               
                 CASP9 
                 842 
                 NM_001229 
                 Caspase 9, apoptosis-related cysteine peptidase 
                 Apoptosis 
               
               
                 CBX3 
                 11335 
                 BX647444 
                 chromobox homolog 3 (HP1 gamma homolog,  Drosophila ) 
                 DNA Damage Repair 
               
               
                 CCNA1 
                 8900 
                 NM_003914 
                 Cyclin A1 
                 Cell Cycle 
               
               
                 CCNA2 
                 890 
                 NM_001237 
                 Cyclin A2 
                 Cell Cycle 
               
               
                 CCNB1 
                 891 
                 NM_031966 
                 Cyclin B1 
                 Cell Cycle 
               
               
                 CCNC 
                 892 
                 NM_005190 
                 Cyclin C 
                 Cell Cycle 
               
               
                 CCND1 
                 595 
                 NM_053056 
                 Cyclin D1 
                 Drug Resistance 
               
               
                 CCND2 
                 894 
                 NM_001759 
                 Cyclin D2 
                 Cell Cycle 
               
               
                 CCNE1 
                 898 
                 NM_001238 
                 Cyclin E1 
                 Drug Resistance 
               
               
                 CCNF 
                 899 
                 NM_001761 
                 Cyclin F 
                 Cell Cycle 
               
               
                 CCNG1 
                 900 
                 NM_004060 
                 Cyclin G1 
                 Cell Cycle 
               
               
                 CCT4 
                 10575 
                 NM_006430 
                 chaperonin containing TCP1, subunit 4 (delta) 
                 DNA Damage Repair 
               
               
                 CCT5 
                 22948 
                 NM_012073 
                 chaperonin containing TCP1, subunit 5 (epsilon) 
                 DNA Damage Repair 
               
               
                 CD27 
                 939 
                 NM_001242 
                 CD27 molecule 
                 Apoptosis 
               
               
                 CD40 
                 958 
                 NM_001250 
                 CD40 molecule, TNF receptor superfamily member 5 
                 Apoptosis 
               
               
                 CD40LG 
                 959 
                 NM_000074 
                 CD40 ligand (TNF superfamily, member 5, hyper-IgM syndrome) 
                 Apoptosis 
               
               
                 CDC16 
                 8881 
                 NM_003903 
                 Cell division cycle 16 homolog ( S. cerevisiae ) 
                 Cell Cycle 
               
               
                 CDC2 
                 983 
                 NM_001786 
                 Cell division cycle 2, G1 to S and G2 to M 
                 p53 Pathway 
               
               
                 CDC20 
                 991 
                 NM_001255 
                 Cell division cycle 20 homolog ( S. cerevisiae ) 
                 Cell Cycle 
               
               
                 CDC25A 
                 993 
                 NM_001789 
                 Cell division cycle 25 homolog A ( S. pombe ) 
                 p53 Pathway 
               
               
                 CDC25C 
                 995 
                 NM_001790 
                 Cell division cycle 25 homolog C ( S. pombe ) 
                 p53 Pathway 
               
               
                 CDC34 
                 997 
                 NM_004359 
                 Cell division cycle 34 homolog ( S. cerevisiae ) 
                 Cell Cycle 
               
               
                 CDC37 
                 11140 
                 NM_007065 
                 Cell division cycle 37 homolog ( S. cerevisiae ) 
                 Cell Cycle 
               
               
                 CDC6 
                 990 
                 NM_001254 
                 Cell division cycle 6 homolog ( S. cerevisiae ) 
                 Cell Cycle 
               
               
                 CDC7 
                 8317 
                 NM_003503 
                 Cell division cycle 7 homolog ( S. cerevisiae ) 
                 Cell Cycle 
               
               
                 CDK2 
                 1017 
                 NM_001798 
                 Cyclin-dependent kinase 2 
                 Drug Resistance 
               
               
                 CDK4 
                 1019 
                 NM_000075 
                 Cyclin-dependent kinase 4 
                 Drug Resistance 
               
               
                 CDK7 
                 1022 
                 NM_001799 
                 cyclin-dependent kinase 7 
                 NER 
               
               
                 CDK8 
                 1024 
                 NM_001260 
                 Cyclin-dependent kinase 8 
                 Cell Cycle 
               
               
                 CDKN1A 
                 1026 
                 NM_000389 
                 Cyclin-dependent kinase inhibitor 1A (p21, Cip1) 
                 Drug Resistance 
               
               
                 CDKN1B 
                 1027 
                 NM_004064 
                 Cyclin-dependent kinase inhibitor 1B (p27, Kip1) 
                 Drug Resistance 
               
               
                 CDKN1C 
                 1028 
                 NM_000076 
                 Cyclin-dependent kinase inhibitor 1C (p57, Kip2) 
                 Cell Cycle 
               
               
                 CDKN2A 
                 1029 
                 NM_000077 
                 Cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) 
                 Drug Resistance 
               
               
                 CDKN2B 
                 1030 
                 NM_004936 
                 Cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4) 
                 Cell Cycle 
               
               
                 CDKN2C 
                 1031 
                 NM_078626 
                 Cyclin-dependent kinase inhibitor 2C (p18, inhibits CDK4) 
                 Cell Cycle 
               
               
                 CDKN2D 
                 1032 
                 NM_001800 
                 Cyclin-dependent kinase inhibitor 2D (p19, inhibits CDK4) 
                 Drug Resistance 
               
               
                 CDKN3 
                 1033 
                 BQ056337 
                 cyclin-dependent kinase inhibitor 3 (CDK2-associated dual 
                 DNA Damage Repair 
               
               
                   
                   
                   
                 specificity phosphatase) 
               
               
                 CETN2 
                 1069 
                 BG567463 
                 centrin, EF-hand protein, 2 
                 NER 
               
               
                 CFLAR 
                 8837 
                 NM_003879 
                 CASP8 and FADD-like apoptosis regulator 
                 Apoptosis 
               
               
                 CHAF1A 
                 10036 
                 NM_005483 
                 chromatin assembly factor 1, subunit A (p150) 
                 DNA Damage Repair 
               
               
                 CHEK1 
                 1111 
                 NM_001274 
                 CHK1 checkpoint homolog ( S. pombe ) 
                 p53 Pathway 
               
               
                 CHEK2 
                 11200 
                 NM_007194 
                 CHK2 checkpoint homolog ( S. pombe ) 
                 p53 Pathway 
               
               
                 CIDEA 
                 1149 
                 NM_001279 
                 Cell death-inducing DFFA-like effector a 
                 Apoptosis 
               
               
                 CIDEB 
                 27141 
                 NM_014430 
                 Cell death-inducing DFFA-like effector b 
                 Apoptosis 
               
               
                 CKS1B 
                 1163 
                 NM_001826 
                 CDC28 protein kinase regulatory subunit 1B 
                 Cell Cycle 
               
               
                 CKS2 
                 1164 
                 BQ898943 
                 CDC28 protein kinase regulatory subunit 2 
                 DNA Damage Repair 
               
               
                 CLPTM1L 
                 81037 
                 NM_030782 
                 CLPTM1-like 
                 Drug Resistance 
               
               
                 COL1A2 
                 1278 
                 J03464 
                 collagen, type I, alpha 2 
                 DNA Damage Repair 
               
               
                 COPB2 
                 9276 
                 AK128561 
                 coatomer protein complex, subunit beta 2 (beta prime) 
                 DNA Damage Repair 
               
               
                 CRADD 
                 8738 
                 NM_003805 
                 CASP2 and RIPK1 domain containing adaptor with death domain 
                 Apoptosis 
               
               
                 CRIP2 
                 1397 
                 AK091845 
                 cysteine-rich protein 2 
                 DNA Damage Repair 
               
               
                 CUL1 
                 8454 
                 NM_003592 
                 Cullin 1 
                 Cell Cycle 
               
               
                 CUL2 
                 8453 
                 NM_003591 
                 Cullin 2 
                 Cell Cycle 
               
               
                 CUL3 
                 8452 
                 NM_003590 
                 Cullin 3 
                 Cell Cycle 
               
               
                 CUL4A 
                 8451 
                 NM_003589 
                 Cullin 4A 
                 Cell Cycle 
               
               
                 CUL4B 
                 8450 
                 NM_003588 
                 cullin 4B 
                 NER 
               
               
                 CUL5 
                 8065 
                 NM_003478 
                 Cullin 5 
                 Cell Cycle 
               
               
                 CYP1A2 
                 1544 
                 NM_000761 
                 Cytochrome P450, family 1, subfamily A, polypeptide 2 
                 Drug Resistance 
               
               
                 CYP3A4 
                 1576 
                 NM_017460 
                 Cytochrome P450, family 3, subfamily A, polypeptide 4 
                 Drug Resistance 
               
               
                 DCLRE1A 
                 9937 
                 D42045 
                 DNA cross-link repair 1A (PSO2 homolog,  S. cerevisiae ) 
                 Apoptosis 
               
               
                 DCLRE1B 
                 64858 
                 NM_022836 
                 DNA cross-link repair 1B (PSO2 homolog,  S. cerevisiae ) 
                 DNA Damage Repair 
               
               
                 DCLRE1C 
                 64421 
                 NM_001033858 
                 DNA cross-link repair 1C (PSO2 homolog,  S. cerevisiae ) 
                 DNA Damage Repair 
               
               
                 DDB1 
                 1642 
                 NM_001923 
                 damage-specific DNA binding protein 1, 127kDa 
                 DNA Damage Repair 
               
               
                 DDB2 
                 1643 
                 AK123492 
                 damage-specific DNA binding protein 2, 48kDa 
                 NER 
               
               
                 DDX11 
                 1663 
                 NM_004399 
                 DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 11 (CHL1-like 
                 NER 
               
               
                   
                   
                   
                 helicase homolog,  S. cerevisiae ) 
               
               
                 DFFA 
                 1676 
                 NM_004401 
                 DNA fragmentation factor, 45kDa, alpha polypeptide 
                 Cell Cycle 
               
               
                 DHFR 
                 1719 
                 NM_000791 
                 Dihydrofolate reductase 
                 Apoptosis 
               
               
                 DIRAS3 
                 9077 
                 NM_004675 
                 DIRAS family, GTP-binding RAS-like 3 
                 Drug Resistance 
               
               
                 DMC1 
                 11144 
                 NM_007068 
                 DMC1 dosage suppressor of mck1 homolog, meiosis-specific 
                 Cell Cycle 
               
               
                   
                   
                   
                 homologous recombination (yeast) 
               
               
                 DNAJC15 
                 29103 
                 NM_013238.2 
                 DNAJC15 DnaJ (Hsp40) homolog, subfamily C, member 15 
                 DNA Damage Repair 
               
               
                 DNM2 
                 1785 
                 NM_004945 
                 Dynamin 2 
                 Cell Cycle 
               
               
                 DNMT1 
                 1786 
                 NM_001379 
                 DNA (cytosine-5-)-methyltransferase 1 
                 p53 Pathway 
               
               
                 DNMT3A 
                 1788 
                 AB208833 
                 DNA (cytosine-5-)-methyltransferase 3 alpha 
                 DNA Damage Repair 
               
               
                 DNMT3B 
                 1789 
                 In multiple clusters 
                 DNA (cytosine-5-)-methyltransferase 3 beta 
                 DNA Damage Repair 
               
               
                 DOT1L 
                 84444 
                 NM_032482 
                 DOT1-like, histone H3 methyltransferase ( S. cerevisiae ) 
                 DNA Damage Repair 
               
               
                 DUT 
                 1854 
                 NM_001025248 
                 dUTP pyrophosphatase 
                 DNA Damage Repair 
               
               
                 DVL3 
                 1857 
                 D86963 
                 dishevelled, dsh homolog 3 ( Drosophila ) 
                 DNA Damage Repair 
               
               
                 E2F2 
                 1870 
                 NM_004091 
                 E2F transcription factor 2 
                 Cell Cycle 
               
               
                 E2F4 
                 1874 
                 NM_001950 
                 E2F transcription factor 4, p107/p130-binding 
                 Cell Cycle 
               
               
                 E2F5 
                 1875 
                 X86097 
                 E2F transcription factor 5, p130-binding 
                 DNA Damage Repair 
               
               
                 E2F6 
                 1876 
                 NM_198256 
                 E2F transcription factor 6 
                 Cell Cycle 
               
               
                 EFNB2 
                 1948 
                 NM_004093 
                 Ephrin-B2 
                 Colon ODX 
               
               
                 EGFR 
                 1956 
                 NM_005228 
                 Epidermal growth factor receptor (erythroblastic leukemia 
                 Drug Resistance 
               
               
                   
                   
                   
                 viral (v-erb-b) oncogene homolog, avian) 
               
               
                 EGR1 
                 1958 
                 NM_001964 
                 Early growth response 1 
                 p53 Pathway 
               
               
                 EHMT1 
                 79813 
                 AB058779 
                 euchromatic histone-lysine N-methyltransferase 1 
                 DNA Damage Repair 
               
               
                 EIF4A3 
                 9775 
                 CR749455 
                 eukaryotic translation initiation factor 4A, isoform 3 
                 DNA Damage Repair 
               
               
                 ELK1 
                 2002 
                 NM_005229 
                 ELK1, member of ETS oncogene family 
                 Drug Resistance 
               
               
                 EME1 
                 146956 
                 BC016470 
                 essential meiotic endonuclease 1 homolog 1 ( S. pombe ) 
                 DNA Damage Repair 
               
               
                 ERBB2 
                 2064 
                 NM_004448 
                 V-erb-b2 erythroblastic leukemia viral oncogene homolog 2, 
                 Drug Resistance 
               
               
                   
                   
                   
                 neuro/glioblastoma derived oncogene homolog (avian) 
               
               
                 ERBB3 
                 2065 
                 NM_001982 
                 V-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) 
                 Drug Resistance 
               
               
                 ERBB4 
                 2066 
                 NM_005235 
                 V-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) 
                 Drug Resistance 
               
               
                 ERCC1 
                 2067 
                 AK092039 
                 excision repair cross-complementing rodent repair 
                 NER 
               
               
                   
                   
                   
                 deficiency, complementation group 1 
               
               
                 ERCC2 
                 2068 
                 AK092872 
                 excision repair cross-complementing rodent repair 
                 NER 
               
               
                   
                   
                   
                 deficiency, complementation group 2 
               
               
                 ERCC3 
                 2071 
                 AK127469 
                 excision repair cross-complementing rodent repair 
                 NER 
               
               
                   
                   
                   
                 deficiency, complementation group 3 
               
               
                 ERCC4 
                 2072 
                 NM_005236 
                 excision repair cross-complementing rodent repair 
                 NER 
               
               
                   
                   
                   
                 deficiency, complementation group 4 
               
               
                 ERCC5 
                 2073 
                 NM_000123 
                 excision repair cross-complementing rodent repair 
                 NER 
               
               
                   
                   
                   
                 deficiency, complementation group 5 
               
               
                 ERCC6 
                 2074 
                 Data not found 
                 excision repair cross-complementing rodent repair 
                 NER 
               
               
                   
                   
                   
                 deficiency, complementation group 6 
               
               
                 ERCC8 
                 1161 
                 AK226129 
                 excision repair cross-complementing rodent repair 
                 NER 
               
               
                   
                   
                   
                 deficiency, complementation group 8 
               
               
                 ESR1 
                 2099 
                 NM_000125 
                 Estrogen receptor 1 
                 Drug Resistance 
               
               
                 ESR2 
                 2100 
                 NM_001437 
                 Estrogen receptor 2 (ER beta) 
                 Drug Resistance 
               
               
                 EXO1 
                 9156 
                 NM_130398 
                 exonuclease 1 
                 DNA Damage Repair 
               
               
                 EZH2 
                 2146 
                 AB208895 
                 enhancer of zeste homolog 2 ( Drosophila ) 
                 DNA Damage Repair 
               
               
                 FADD 
                 8772 
                 NM_003824 
                 Fas (TNFRSF6)-associated via death domain 
                 Apoptosis 
               
               
                 FANCA 
                 2175 
                 X99226 
                 Fanconi anemia, complementation group A 
                 DNA Damage Repair 
               
               
                 FANCB 
                 2187 
                 NM_001018113 
                 Fanconi anemia, complementation group B 
                 DNA Damage Repair 
               
               
                 FANCC 
                 2176 
                 NM_000136 
                 Fanconi anemia, complementation group C 
                 DNA Damage Repair 
               
               
                 FANCD2 
                 2177 
                 BC038666 
                 Fanconi anemia, complementation group D2 
                 DNA Damage Repair 
               
               
                 FANCE 
                 2178 
                 BC046359 
                 Fanconi anemia, complementation group E 
                 DNA Damage Repair 
               
               
                 FANCF 
                 2188 
                 NM_022725 
                 Fanconi anemia, complementation group F 
                 DNA Damage Repair 
               
               
                 FANCG 
                 2189 
                 AJ007669 
                 Fanconi anemia, complementation group G 
                 DNA Damage Repair 
               
               
                 FANCL 
                 55120 
                 BC037570 
                 Fanconi anemia, complementation group L 
                 DNA Damage Repair 
               
               
                 FANCM 
                 57697 
                 NM_020937 
                 Fanconi anemia, complementation group M 
                 DNA Damage Repair 
               
               
                 FAP 
                 2191 
                 U09278 
                 fibroblast activation protein, alpha 
                 DNA Damage Repair 
               
               
                 FAS 
                 355 
                 NM_000043 
                 Fas (TNF receptor superfamily, member 6) 
                 Apoptosis 
               
               
                 FASLG 
                 356 
                 NM_000639 
                 Fas ligand (TNF superfamily, member 6) 
                 Apoptosis 
               
               
                 FEN1 
                 2237 
                 NM_004111 
                 flap structure-specific endonuclease 1 
                 DNA Damage Repair 
               
               
                 FGF2 
                 2247 
                 NM_002006 
                 Fibroblast growth factor 2 (basic) 
                 Drug Resistance 
               
               
                 FLJ35220 
                 284131 
                 NM_173627 
                 hypothetical protein FLJ35220 
                 DNA Damage Repair 
               
               
                 FOS 
                 2353 
                 NM_005252 
                 V-fos FBJ murine osteosarcoma viral oncogene homolog 
                 Drug Resistance 
               
               
                 G3BP1 
                 10146 
                 NM_005754 
                 GTPase activating protein (SH3 domain) binding protein 1 
                 DNA Damage Repair 
               
               
                 GADD45A 
                 1647 
                 NM_001924 
                 Growth arrest and DNA-damage-inducible, alpha 
                 Apoptosis 
               
               
                 GADD45B 
                 4616 
                 AF087853 
                 Growth arrest and DNA-damage-inducible, beta 
                 Colon ODX 
               
               
                 GGT1 
                 2678 
                 NM_005265 
                 Gamma-glutamyltransferase 1 
                 Drug Metabolism 
               
               
                 GPX1 
                 2876 
                 NM_000581 
                 Glutathione peroxidase 1 
                 Drug Metabolism 
               
               
                 GPX2 
                 2877 
                 NM_002083 
                 Glutathione peroxidase 2 (gastrointestinal) 
                 Drug Metabolism 
               
               
                 GPX3 
                 2878 
                 NM_002084 
                 Glutathione peroxidase 3 (plasma) 
                 Drug Metabolism 
               
               
                 GPX4 
                 2879 
                 NM_002085 
                 Glutathione peroxidase 4 (phospholipid hydroperoxidase) 
                 Drug Metabolism 
               
               
                 GPX5 
                 2880 
                 NM_001509 
                 Glutathione peroxidase 5 (epididymal androgen-related protein) 
                 Drug Metabolism 
               
               
                 GSK3A 
                 2931 
                 NM_019884 
                 Glycogen synthase kinase 3 alpha 
                 Drug Resistance 
               
               
                 GSR 
                 2936 
                 NM_000637 
                 Glutathione reductase 
                 Drug Metabolism 
               
               
                 GSTA3 
                 2940 
                 NM_000847 
                 Glutathione S-transferase A3 
                 Drug Metabolism 
               
               
                 GSTA4 
                 2941 
                 NM_001512 
                 Glutathione S-transferase A4 
                 Drug Metabolism 
               
               
                 GSTM2 
                 2946 
                 NM_000848 
                 Glutathione S-transferase M2 (muscle) 
                 Drug Metabolism 
               
               
                 GSTM3 
                 2947 
                 NM_000849 
                 Glutathione S-transferase M3 (brain) 
                 Drug Metabolism 
               
               
                 GSTM5 
                 2949 
                 NM_000851 
                 Glutathione S-transferase M5 
                 Drug Metabolism 
               
               
                 GSTP1 
                 2950 
                 NM_000852 
                 Glutathione S-transferase pi 
                 Drug Metabolism 
               
               
                 GSTT1 
                 2952 
                 NM_000853 
                 Glutathione S-transferase theta 1 
                 Drug Metabolism 
               
               
                 GSTZ1 
                 2954 
                 NM_001513 
                 Glutathione transferase zeta 1 (maleylacetoacetate isomerase) 
                 Drug Metabolism 
               
               
                 GTF2H1 
                 2965 
                 NM_005316 
                 general transcription factor IIH, polypeptide 1, 62 kDa 
                 NER 
               
               
                 GTF2H2 
                 2966 
                 BX647532 
                 general transcription factor IIH, polypeptide 2, 44 kDa 
                 NER 
               
               
                 GTF2H3 
                 2967 
                 BC039726 
                 general transcription factor IIH, polypeptide 3, 34 kDa 
                 NER 
               
               
                 GTF2H4 
                 2968 
                 NM_001517 
                 general transcription factor IIH, polypeptide 4, 52 kDa 
                 NER 
               
               
                 GTF2H5 
                 404672 
                 AK055106 
                 general transcription factor IIH, polypeptide 5 
                 NER 
               
               
                 H2AFX 
                 3014 
                 BM917453 
                 H2A histone family, member X 
                 DNA Damage Repair 
               
               
                 H2AFZ 
                 3015 
                 AK056803 
                 H2A histone family, member Z 
                 DNA Damage Repair 
               
               
                 HDAC10 
                 83933 
                 NM_032019 
                 histone deacetylase 10 
                 DNA Damage Repair 
               
               
                 HDAC11 
                 79885 
                 AL834223 
                 histone deacetylase 11 
                 DNA Damage Repair 
               
               
                 HDAC2 
                 3066 
                 NM_001527 
                 histone deacetylase 2 
                 DNA Damage Repair 
               
               
                 HDAC4 
                 9759 
                 NM_006037 
                 histone deacetylase 4 
                 DNA Damage Repair 
               
               
                 HDAC6 
                 10013 
                 BC069243 
                 histone deacetylase 6 
                 DNA Damage Repair 
               
               
                 HEL308 
                 113510 
                 NM_133636 
                 DNA helicase HEL308 
                 DNA Damage Repair 
               
               
                 HERC5 
                 51191 
                 NM_016323 
                 Hect domain and RLD 5 
                 Cell Cycle 
               
               
                 HES1 
                 3280 
                 NM_005524.2 
                 Hairy and enhancer of split 1, ( Drosophila ) 
                 Notch Pathway 
               
               
                 HIF1A 
                 3091 
                 NM_001530 
                 Hypoxia-inducible factor 1, alpha subunit (basic helix- 
                 Drug Resistance 
               
               
                   
                   
                   
                 loop-helix transcription factor) 
               
               
                 HLTF 
                 6596 
                 NM_003071 
                 helicase-like transcription factor 
                 DNA Damage Repair 
               
               
                 HMG20B 
                 10362 
                 NM_006339.2 
                 HMG20B high-mobility group 20B 
                 DNA Damage Repair 
               
               
                 HNRPA2B1 
                 3181 
                 NM_031243 
                 heterogeneous nuclear ribonucleoprotein A2/B1 
                 Apoptosis 
               
               
                 HRK 
                 8739 
                 NM_003806 
                 Harakiri, BCL2 interacting protein (contains only BH3 domain) 
                 DNA Damage Repair 
               
               
                 HSP90B1 
                 7184 
                 AB209534 
                 heat shock protein 90 kDa beta (Grp94), member 1 
                 DNA Damage Repair 
               
               
                 HSPD1 
                 3329 
                 NM_002156 
                 heat shock 60 kDa protein 1 (chaperonin) 
                 Colon ODX 
               
               
                 HSPE1 
                 3336 
                 BU517060 
                 Heat shock 10 kDa protein 1 (chaperonin 10) 
                 DNA Damage Repair 
               
               
                 HSPE1 
                 3336 
                 BU517060 
                 heat shock 10 kDa protein 1 (chaperonin 10) 
                 DNA Damage Repair 
               
               
                 HUS1 
                 3364 
                 CR619988 
                 HUS1 checkpoint homolog ( S. pombe ) 
                 DNA Damage Repair 
               
               
                 IARS 
                 3376 
                 NM_013417 
                 isoleucyl-tRNA synthetase 
                 p53 Pathway 
               
               
                 IFNB1 
                 3456 
                 NM_002176 
                 Interferon, beta 1, fibroblast 
                 DNA Damage Repair 
               
               
                 IFNGR2 
                 3460 
                 NM_005534 
                 interferon gamma receptor 2 (interferon gamma transducer 1) 
                 Drug Resistance 
               
               
                 IGF1R 
                 3480 
                 NM_000875 
                 Insulin-like growth factor 1 receptor 
                 Drug Resistance 
               
               
                 IGF2R 
                 3482 
                 NM_000876 
                 Insulin-like growth factor 2 receptor 
                 p53 Pathway 
               
               
                 IL6 
                 3569 
                 NM_000600 
                 Interleukin 6 (interferon, beta 2) 
                 Cell Cycle 
               
               
                 IL8 
                 3576 
                 NM_000584 
                 Interleukin 8 
                 DNA Damage Repair 
               
               
                 ILF2 
                 3608 
                 BG121872 
                 interleukin enhancer binding factor 2, 45 kDa 
                 Colon ODX 
               
               
                 INHBA 
                 3624 
                 BX648811 
                 Inhibin, beta A 
                 p53 Pathway 
               
               
                 JUN 
                 3725 
                 NM_002228 
                 Jun oncogene 
                 DNA Damage Repair 
               
               
                 KDELR2 
                 11014 
                 NM_006854 
                 KDEL (Lys-Asp-Glu-Leu) endoplasmic reticulum 
                 DNA Damage Repair 
               
               
                   
                   
                   
                 protein retention receptor 2 
               
               
                 KIAA0101 
                 9768 
                 AY358648 
                 KIAA0101 
                 Cell Cycle 
               
               
                 KNTC1 
                 9735 
                 NM_014708 
                 Kinetochore associated 1 
                 DNA Damage Repair 
               
               
                 KPNA2 
                 3838 
                 BC067848 
                 karyopherin alpha 2 (RAG cohort 1, importin alpha 1) 
                 p53 Pathway 
               
               
                 KRAS 
                 3845 
                 NM_004985 
                 V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog 
                 DNA Damage Repair 
               
               
                 LDHA 
                 3939 
                 NM_005566 
                 lactate dehydrogenase A 
                 NER 
               
               
                 LIG1 
                 3978 
                 AB208791 
                 ligase I, DNA, ATP-dependent 
                 DNA Damage Repair 
               
               
                 LIG3 
                 3980 
                 NM_013975 
                 ligase III, DNA, ATP-dependent 
                 DNA Damage Repair 
               
               
                 LIG4 
                 3981 
                 NM_002312 
                 ligase IV, DNA, ATP-dependent 
                 Apoptosis 
               
               
                 LTA 
                 4049 
                 NM_000595 
                 Lymphotoxin alpha (TNF superfamily, member 1) 
                 Apoptosis 
               
               
                 LTBR 
                 4055 
                 NM_002342 
                 Lymphotoxin beta receptor (TNFR superfamily, member 3) 
                 Cell Cycle 
               
               
                 MAD2L1 
                 4085 
                 NM_002358 
                 MAD2 mitotic arrest deficient-like 1 (yeast) 
                 DNA Damage Repair 
               
               
                 MAD2L2 
                 10459 
                 AK094316 
                 MAD2 mitotic arrest deficient-like 2 (yeast) 
                 DNA Damage Repair 
               
               
                 MBD1 
                 4152 
                 NM_015846 
                 methyl-CpG binding domain protein 1 
                 DNA Damage Repair 
               
               
                 MBD2 
                 8932 
                 NM_003927 
                 methyl-CpG binding domain protein 2 
                 DNA Damage Repair 
               
               
                 MBD3 
                 53615 
                 NM_003926 
                 methyl-CpG binding domain protein 3 
                 DNA Damage Repair 
               
               
                 MBD4 
                 8930 
                 AF072250 
                 methyl-CpG binding domain protein 4 
                 Apoptosis 
               
               
                 MCL1 
                 4170 
                 NM_021960 
                 Myeloid cell leukemia sequence 1 (BCL2-related) 
                 Cell Cycle 
               
               
                 MCM2 
                 4171 
                 NM_004526 
                 Minichromosome maintenance complex component 2 
                 DNA Damage Repair 
               
               
                 MCM3 
                 4172 
                 NM_002388 
                 minichromosome maintenance complex component 3 
                 Cell Cycle 
               
               
                 MCM4 
                 4173 
                 NM_005914 
                 Minichromosome maintenance complex component 4 
                 Cell Cycle 
               
               
                 MCM5 
                 4174 
                 NM_006739 
                 Minichromosome maintenance complex component 5 
                 Cell Cycle 
               
               
                 MCM6 
                 4175 
                 NM_005915 
                 Minichromosome maintenance complex component 6 
                 Cell Cycle 
               
               
                 MCM7 
                 4176 
                 NM_005916 
                 Minichromosome maintenance complex component 7 
                 p53 Pathway 
               
               
                 MDM2 
                 4193 
                 NM_002392 
                 Mdm2, transformed 3T3 cell double minute 2, p53 
                 DNA Damage Repair 
               
               
                   
                   
                   
                 binding protein (mouse) 
               
               
                 MECP2 
                 4204 
                 NM_004992 
                 methyl CpG binding protein 2 (Rett syndrome) 
                 Drug Resistance 
               
               
                 MET 
                 4233 
                 NM_000245 
                 Met proto-oncogene (hepatocyte growth factor receptor) 
                 DNA Damage Repair 
               
               
                 MGMT 
                 4255 
                 CR618411 
                 O-6-methylguanine-DNA methyltransferase 
                 Drug Metabolism 
               
               
                 MGST1 
                 4257 
                 NM_020300 
                 Microsomal glutathione S-transferase 1 
                 Drug Metabolism 
               
               
                 MGST2 
                 4258 
                 NM_002413 
                 Microsomal glutathione S-transferase 2 
                 Drug Metabolism 
               
               
                 MGST3 
                 4259 
                 NM_004528 
                 Microsomal glutathione S-transferase 3 
                 Cell Cycle 
               
               
                 MKI67 
                 4288 
                 NM_002417 
                 Antigen identified by monoclonal antibody Ki-67 
                 p53 Pathway 
               
               
                 MLH1 
                 4292 
                 NM_000249 
                 MutL homolog 1, colon cancer, nonpolyposis type 2 ( E. coli ) 
                 DNA Damage Repair 
               
               
                 MLH3 
                 27030 
                 NM_001040108 
                 mutL homolog 3 ( E. coli ) 
                 DNA Damage Repair 
               
               
                 MLL 
                 4297 
                 NM_005933 
                 myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, 
                 DNA Damage Repair 
               
               
                   
                   
                   
                   Drosophila ) 
               
               
                 MMP9 
                 4318 
                 NM_004994 
                 matrix metallopeptidase 9 (gelatinase B, 92 kDa gelatinase, 92 kDa 
                 DNA Damage Repair 
               
               
                   
                   
                   
                 type IV collagenase) 
               
               
                 MMS19L 
                 64210 
                 NM_022362 
                 MMS19-like (MET18 homolog,  S. cerevisiae ) 
                 NER 
               
               
                 MNAT1 
                 4331 
                 NM_002431 
                 menage a trois homolog 1, cyclin H assembly factor 
                 DNA Damage Repair 
               
               
                 MPG 
                 4350 
                 BF572325 
                 N-methylpurine-DNA glycosylase 
                 DNA Damage Repair 
               
               
                 MRE11A 
                 4361 
                 NM_005590 
                 MRE11 meiotic recombination 11 homolog A ( S. cerevisiae ) 
                 DNA Damage Repair 
               
               
                 MRPL3 
                 11222 
                 BM541805 
                 mitochondrial ribosomal protein L3 
                 DNA Damage Repair 
               
               
                 MRPS12 
                 6183 
                 BU149479 
                 mitochondrial ribosomal protein S12 
                 p53 Pathway 
               
               
                 MSH2 
                 4436 
                 NM_000251 
                 MutS homolog 2, colon cancer, nonpolyposis type 1 ( E. coli ) 
                 DNA Damage Repair 
               
               
                 MSH3 
                 4437 
                 NM_002439 
                 mutS homolog 3 ( E. coli ) 
                 DNA Damage Repair 
               
               
                 MSH4 
                 4438 
                 BC033030 
                 mutS homolog 4 ( E. coli ) 
                 DNA Damage Repair 
               
               
                 MSH5 
                 4439 
                 AB209886 
                 mutS homolog 5 ( E. coli ) 
                 DNA Damage Repair 
               
               
                 MSH6 
                 2956 
                 NM_000179 
                 mutS homolog 6 ( E. coli ) 
                 Drug Metabolism 
               
               
                 MT2A 
                 4502 
                 NM_005953 
                 Metallothionein 2A 
                 Drug Metabolism 
               
               
                 MT3 
                 4504 
                 NM_005954 
                 Metallothionein 3 
                 DNA Damage Repair 
               
               
                 MTHFD2 
                 10797 
                 NM_001040409 
                 methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 2, 
                 Drug Metabolism 
               
               
                   
                   
                   
                 methenyltetrahydrofolate cyclohydrolase 
               
               
                 MTHFR 
                 4524 
                 NM_005957 
                 5,10-methylenetetrahydrofolate reductase (NADPH) 
                 DNA Damage Repair 
               
               
                 MUS81 
                 80198 
                 NM_025128 
                 MUS81 endonuclease homolog ( S. cerevisiae ) 
                 DNA Damage Repair 
               
               
                 MUTYH 
                 4595 
                 NM_012222 
                 mutY homolog ( E. coli ) 
                 Drug Resistance 
               
               
                 MVP 
                 9961 
                 NM_017458 
                 Major vault protein 
                 Colon ODX 
               
               
                 MYBL2 
                 4605 
                 BX647151 
                 V-myb myeloblastosis viral oncogene homolog (avian)-like 2 
                 p53 Pathway 
               
               
                 MYC 
                 4609 
                 NM_002467 
                 V-myc myelocytomatosis viral oncogene homolog (avian) 
                 Apoptosis 
               
               
                 NAIP 
                 4671 
                 NM_004536 
                 NLR family, apoptosis inhibitory protein 
                 DNA Damage Repair 
               
               
                 NBN 
                 4683 
                 BX640816 
                 Nibrin 
                 DNA Damage Repair 
               
               
                 NCBP2 
                 22916 
                 AK093216 
                 nuclear cap binding protein subunit 2, 20 kDa 
                 Notch Pathway 
               
               
                 NCSTN 
                 23385 
                 NM_015331.2 
                 Nicastrin 
                 DNA Damage Repair 
               
               
                 NEIL1 
                 79661 
                 AK097008 
                 nei endonuclease VIII-like 1 ( E. coli ) 
                 DNA Damage Repair 
               
               
                 NEIL2 
                 252969 
                 AK056206 
                 nei like 2 ( E. coli ) 
                 DNA Damage Repair 
               
               
                 NEIL3 
                 55247 
                 NM_018248 
                 nei endonuclease VIII-like 3 ( E. coli ) 
                 p53 Pathway 
               
               
                 NF1 
                 4763 
                 NM_000267 
                 Neurofibromin 1 (neurofibromatosis, von Recklinghausen 
                 Drug Resistance 
               
               
                   
                   
                   
                 disease, Watson disease) 
               
               
                 NFKB1 
                 4790 
                 NM_003998 
                 Nuclear factor of kappa light polypeptide gene enhancer 
                 Drug Resistance 
               
               
                   
                   
                   
                 in B-cells 1 (p105) 
               
               
                 NFKB2 
                 4791 
                 NM_002502 
                 Nuclear factor of kappa light polypeptide gene enhancer 
                 Drug Resistance 
               
               
                   
                   
                   
                 in B-cells 2 (p49/p100) 
               
               
                 NFKBIB 
                 4793 
                 NM_002503 
                 Nuclear factor of kappa light polypeptide gene enhancer 
                 Drug Resistance 
               
               
                   
                   
                   
                 in B-cells inhibitor, beta 
               
               
                 NFKBIE 
                 4794 
                 NM_004556 
                 Nuclear factor of kappa light polypeptide gene enhancer 
                 DNA Damage Repair 
               
               
                   
                   
                   
                 in B-cells inhibitor, epsilon 
               
               
                 NHEJ1 
                 79840 
                 NM_024782 
                 nonhomologous end-joining factor 1 
                 DNA Damage Repair 
               
               
                 NME1 
                 4830 
                 BG114681 
                 non-metastatic cells 1, protein (NM23A) expressed in 
                 Apoptosis 
               
               
                 NOD1 
                 10392 
                 NM_006092 
                 Nucleotide-binding oligomerization domain containing 1 
                 Apoptosis 
               
               
                 NOL3 
                 8996 
                 NM_003946 
                 Nucleolar protein 3 (apoptosis repressor with CARD domain) 
                 DNA Damage Repair 
               
               
                 NONO 
                 4841 
                 NM_007363 
                 non-POU domain containing, octamer-binding 
                 Notch Pathway 
               
               
                 NOTCH1 
                 4851 
                 NM_017617 
                 NOTCH 1 Notch homolog 1, translocation-associated ( Drosophila ) 
                 DNA Damage Repair 
               
               
                 NTHL1 
                 4913 
                 BQ067653 
                 nth endonuclease Ill-like 1 ( E. coli ) 
                 DNA Damage Repair 
               
               
                 NUDT1 
                 4521 
                 BM455743 
                 nudix (nucleoside diphosphate linked moiety X)-type motif 1 
                 Notch Pathway 
               
               
                 NUMB 
                 8650 
                 NM_001005743.1 
                 Numb homolog ( Drosophila ) 
                 DNA Damage Repair 
               
               
                 NUP205 
                 23165 
                 BC146784 
                 nucleoporin 205 kDa 
                 DNA Damage Repair 
               
               
                 OGG1 
                 4968 
                 NM_016819 
                 8-oxoguanine DNA glycosylase 
                 DNA Damage Repair 
               
               
                 OGT 
                 8473 
                 AL050366 
                 O-linked N-acetylglucosamine (GlcNAc) transferase (UDP-N- 
                 p53 Pathway 
               
               
                   
                   
                   
                 acetylglucosamine:polypeptide-N-acetylglucosaminyl transferase) 
               
               
                 P53AIP1 
                 63970 
                 NM_022112 
                 P53-regulated apoptosis-inducing protein 1 
                 DNA Damage Repair 
               
               
                 PAFAH1B3 
                 5050 
                 BM904583 
                 platelet-activating factor acetylhydrolase, isoform 
                 DNA Damage Repair 
               
               
                   
                   
                   
                 Ib, gamma subunit 29 kDa 
               
               
                 PAICS 
                 10606 
                 In multiple clusters 
                 phosphoribosylaminoimidazole carboxylase, 
                 DNA Damage Repair 
               
               
                   
                   
                   
                 phosphoribosylaminoimidazole succinocarboxamide synthetase 
               
               
                 PARP1 
                 142 
                 NM_001618 
                 poly (ADP-ribose) polymerase family, member 1 
                 DNA Damage Repair 
               
               
                 PARP2 
                 10038 
                 AK001980 
                 poly (ADP-ribose) polymerase family, member 2 
                 p53 Pathway 
               
               
                 PCNA 
                 5111 
                 NM_182649 
                 Proliferating cell nuclear antigen 
                 Cell Cycle 
               
               
                 PKMYT1 
                 9088 
                 NM_182687 
                 Protein kinase, membrane associated tyrosine/threonine 1 
                 DNA Damage Repair 
               
               
                 PMS1 
                 5378 
                 CR749432 
                 PMS1 postmeiotic segregation increased 1 ( S. cerevisiae ) 
                 DNA Damage Repair 
               
               
                 PMS2 
                 5395 
                 NM_000535 
                 PMS2 postmeiotic segregation increased 2 ( S. cerevisiae ) 
                 DNA Damage Repair 
               
               
                 PMS2L3 
                 5387 
                 CR621744 
                 postmeiotic segregation increased 2-like 3 
                 DNA Damage Repair 
               
               
                 POLB 
                 5423 
                 CR627365 
                 polymerase (DNA directed), beta 
                 DNA Damage Repair 
               
               
                 POLD1 
                 5424 
                 AB209560 
                 polymerase (DNA directed), delta 1, catalytic subunit 125 kDa 
                 DNA Damage Repair 
               
               
                 POLD3 
                 10714 
                 NM_006591 
                 polymerase (DNA-directed), delta 3, accessory subunit 
                 DNA Damage Repair 
               
               
                 POLE 
                 5426 
                 In multiple clusters 
                 polymerase (DNA directed), epsilon 
                 NER 
               
               
                 POLE3 
                 54107 
                 AK092840 
                 polymerase (DNA directed), epsilon 3 (p17 subunit) 
                 DNA Damage Repair 
               
               
                 POLG 
                 5428 
                 BC050559 
                 polymerase (DNA directed), gamma 
                 NER 
               
               
                 POLH 
                 5429 
                 NM_006502 
                 polymerase (DNA directed), eta 
                 DNA Damage Repair 
               
               
                 POLI 
                 11201 
                 NM_007195 
                 polymerase (DNA directed) iota 
                 DNA Damage Repair 
               
               
                 POLK 
                 51426 
                 BC041798 
                 polymerase (DNA directed) kappa 
                 DNA Damage Repair 
               
               
                 POLL 
                 27343 
                 AK128521 
                 polymerase (DNA directed), lambda 
                 DNA Damage Repair 
               
               
                 POLM 
                 27434 
                 BC026306 
                 polymerase (DNA directed), mu 
                 DNA Damage Repair 
               
               
                 POLN 
                 353497 
                 AK131239 
                 polymerase (DNA directed) nu 
                 DNA Damage Repair 
               
               
                 POLQ 
                 10721 
                 AY032677 
                 polymerase (DNA directed), theta 
                 DNA Damage Repair 
               
               
                 PPARA 
                 5465 
                 NM_005036 
                 Peroxisome proliferative activated receptor, alpha 
                 DNA Damage Repair 
               
               
                 PPARD 
                 5467 
                 NM_006238 
                 Peroxisome proliferator-activated receptor delta 
                 Drug Resistance 
               
               
                 PPARG 
                 5468 
                 NM_015869 
                 Peroxisome proliferator-activated receptor gamma 
                 Drug Resistance 
               
               
                 PPP2R5C 
                 5527 
                 NM_002719 
                 protein phosphatase 2, regulatory subunit B′, gamma isoform 
                 Drug Resistance 
               
               
                 PRDX2 
                 7001 
                 BM805899 
                 peroxiredoxin 2 
                 DNA Damage Repair 
               
               
                 PRDX4 
                 10549 
                 CD579519 
                 peroxiredoxin 4 
                 DNA Damage Repair 
               
               
                 PRKDC 
                 5591 
                 NM_006904 
                 protein kinase, DNA-activated, catalytic polypeptide 
                 DNA Damage Repair 
               
               
                 PRMT1 
                 3276 
                 CR622298 
                 protein arginine methyltransferase 1 
                 DNA Damage Repair 
               
               
                 PSEN1 
                 5663 
                 NM_000021.3 
                 Presenilin 1 
                 DNA Damage Repair 
               
               
                 PSMA1 
                 5682 
                 BM455876 
                 proteasome (prosome, macropain) subunit, alpha type, 1 
                 Notch Pathway 
               
               
                 PSMC4 
                 5704 
                 CR611800 
                 proteasome (prosome, macropain) 26S subunit, ATPase, 4 
                 DNA Damage Repair 
               
               
                 PSME2 
                 5721 
                 In multiple clusters 
                 proteasome (prosome, macropain) activator subunit 2 (PA28 beta) 
                 DNA Damage Repair 
               
               
                 PTEN 
                 5728 
                 NM_000314 
                 Phosphatase and tensin homolog (mutated in multiple 
                 DNA Damage Repair 
               
               
                   
                   
                   
                 advanced cancers 1 ) 
               
               
                 PTMA 
                 5757 
                 BM470466 
                 prothymosin, alpha (gene sequence 28) 
                 p53 Pathway 
               
               
                 PTP4A3 
                 11156 
                 NM_007079 
                 PTP4A3 protein tyrosine phosphatase type IVA, member 3 
                 DNA Damage Repair 
               
               
                 PTTG1 
                 9232 
                 NM_004219 
                 Pituitary tumor-transforming 1 
                 BMS Data 
               
               
                 PYCARD 
                 29108 
                 NM_013258 
                 PYD and CARD domain containing 
                 p53 Pathway 
               
               
                 RAD1 
                 5810 
                 NM_133377 
                 RAD1 homolog ( S. pombe ) 
                 Apoptosis 
               
               
                 RAD17 
                 5884 
                 AF076838 
                 RAD17 homolog ( S. pombe ) 
                 DNA Damage Repair 
               
               
                 RAD18 
                 56852 
                 NM_020165 
                 RAD18 homolog ( S. cerevisiae ) 
                 DNA Damage Repair 
               
               
                 RAD23A 
                 5886 
                 BF343783 
                 RAD23 homolog A ( S. cerevisiae ) 
                 DNA Damage Repair 
               
               
                 RAD23B 
                 5887 
                 NM_002874 
                 RAD23 homolog B 
                 DNA Damage Repair 
               
               
                 RAD50 
                 10111 
                 U63139 
                 RAD50 homolog ( S. cerevisiae ) 
                 NER 
               
               
                 RAD51 
                 5888 
                 NM_002875 
                 RAD51 homolog (RecA homolog,  E. coli ) ( S. cerevisiae ) 
                 DNA Damage Repair 
               
               
                 RAD51C 
                 5889 
                 BC073161 
                 RAD51 homolog C ( S. cerevisiae ) 
                 DNA Damage Repair 
               
               
                 RAD51L1 
                 5890 
                 BX248766 
                 RAD51-like 1 ( S. cerevisiae ) 
                 DNA Damage Repair 
               
               
                 RAD51L3 
                 5892 
                 BX647297 
                 RAD51-like 3 ( S. cerevisiae ) 
                 DNA Damage Repair 
               
               
                 RAD52 
                 5893 
                 NM_134424 
                 RAD52 homolog ( S. cerevisiae ) 
                 DNA Damage Repair 
               
               
                 RAD54B 
                 25788 
                 In multiple clusters 
                 RAD54 homolog B ( S. cerevisiae ) 
                 DNA Damage Repair 
               
               
                 RAD54L 
                 8438 
                 NM_003579 
                 RAD54-like ( S. cerevisiae ) 
                 DNA Damage Repair 
               
               
                 RAD9A 
                 5883 
                 NM_004584 
                 RAD9 homolog A ( S. pombe ) 
                 DNA Damage Repair 
               
               
                 RARA 
                 5914 
                 NM_000964 
                 Retinoic acid receptor, alpha 
                 DNA Damage Repair 
               
               
                 RARB 
                 5915 
                 NM_000965 
                 Retinoic acid receptor, beta 
                 Drug Resistance 
               
               
                 RARG 
                 5916 
                 NM_000966 
                 Retinoic acid receptor, gamma 
                 Drug Resistance 
               
               
                 RB1 
                 5925 
                 NM_000321 
                 Retinoblastoma 1 (including osteosarcoma) 
                 Drug Resistance 
               
               
                 RBBP8 
                 5932 
                 NM_002894 
                 Retinoblastoma binding protein 8 
                 Drug Resistance 
               
               
                 RBL1 
                 5933 
                 NM_002895 
                 Retinoblastoma-like 1 (p107) 
                 Cell Cycle 
               
               
                 RBL2 
                 5934 
                 NM_005611 
                 Retinoblastoma-like 2 (p130) 
                 Cell Cycle 
               
               
                 RBM4 
                 5936 
                 AK097592 
                 RNA binding motif protein 4 
                 Cell Cycle 
               
               
                 RBX1 
                 9978 
                 BU 155800 
                 ring-box 1 
                 DNA Damage Repair 
               
               
                 RDM1 
                 201299 
                 NM_145654 
                 RAD52 motif 1 
                 NER 
               
               
                 RECQL 
                 5965 
                 L36140 
                 RecQ protein-like (DNA helicase Q1-like) 
                 DNA Damage Repair 
               
               
                 RECQL4 
                 9401 
                 BC020496 
                 RecQ protein-like 4 
                 DNA Damage Repair 
               
               
                 RECQL5 
                 9400 
                 NM_004259 
                 RecQ protein-like 5 
                 DNA Damage Repair 
               
               
                 RELA 
                 5970 
                 NM_021975 
                 V-rel reticuloendotheliosis viral oncogene homolog A, nuclear factor 
                 DNA Damage Repair 
               
               
                   
                   
                   
                 of kappa light polypeptide gene enhancer in B-cells 3, p65 (avian) 
               
               
                 RELB 
                 5971 
                 NM_006509 
                 V-rel reticuloendotheliosis viral oncogene homolog B, nuclear factor 
                 p53 Pathway 
               
               
                   
                   
                   
                 of kappa light polypeptide gene enhancer in B-cells 3 (avian) 
               
               
                 REV1 
                 51455 
                 NM_016316 
                 REV1 homolog ( S. cerevisiae ) 
                 Drug Resistance 
               
               
                 REV3L 
                 5980 
                 AF078695 
                 REV3-like, catalytic subunit of DNA polymerase zeta (yeast) 
                 DNA Damage Repair 
               
               
                 RFC1 
                 5981 
                 NM_002913 
                 replication factor C (activator 1) 1, 145 kDa 
                 DNA Damage Repair 
               
               
                 RFC4 
                 5984 
                 NM_002916 
                 replication factor C (activator 1) 4, 37 kDa 
                 NER 
               
               
                 RIPK2 
                 8767 
                 NM_003821 
                 Receptor-interacting serine-threonine kinase 2 
                 DNA Damage Repair 
               
               
                 RPA1 
                 6117 
                 NM_002945 
                 replication protein A1, 70 kDa 
                 Apoptosis 
               
               
                 RPA2 
                 6118 
                 NM_002946 
                 replication protein A2, 32 kDa 
                 DNA Damage Repair 
               
               
                 RPA3 
                 6119 
                 NM_002947 
                 replication protein A3, 14 kDa 
                 DNA Damage Repair 
               
               
                 RPA4 
                 29935 
                 U24186 
                 replication protein A4, 34 kDa 
                 DNA Damage Repair 
               
               
                 RPL13 
                 6137 
                 AK095954 
                 ribosomal protein L13 
                 NER 
               
               
                 RPL27 
                 6155 
                 BF219474 
                 ribosomal protein L27 
                 DNA Damage Repair 
               
               
                 RPL35 
                 11224 
                 CR622666 
                 ribosomal protein L35 
                 DNA Damage Repair 
               
               
                 RRM1 
                 6240 
                 NM_001033.3 
                 RRM1 ribonucleotide reductase M1 
                 DNA Damage Repair 
               
               
                 RRM2B 
                 50484 
                 NM_015713 
                 ribonucleotide reductase M2 B (TP53 inducible) 
                 DNA Damage Repair 
               
               
                 RUNX1 
                 861 
                 NM_001001890 
                 Runt-related transcription factor 1 (acute myeloid 
                 Colon ODX 
               
               
                   
                   
                   
                 leukemia 1; aml1 oncogene) 
               
               
                 RXRA 
                 6256 
                 NM_002957 
                 Retinoid X receptor, alpha 
                 Drug Resistance 
               
               
                 RXRB 
                 6257 
                 NM_021976 
                 Retinoid X receptor, beta 
                 Drug Resistance 
               
               
                 SDHC 
                 6391 
                 NM_003001 
                 succinate dehydrogenase complex, subunit C, integral 
                 DNA Damage Repair 
               
               
                   
                   
                   
                 membrane protein, 15 kDa 
               
               
                 SERTAD1 
                 29950 
                 NM_013376 
                 SERTA domain containing 1 
                 Cell Cycle 
               
               
                 SETD7 
                 80854 
                 NM_030648 
                 SET domain containing (lysine methyltransferase) 7 
                 DNA Damage Repair 
               
               
                 SETD8 
                 387893 
                 In multiple clusters 
                 SET domain containing (lysine methyltransferase) 8 
                 DNA Damage Repair 
               
               
                 SHFM1 
                 7979 
                 AK094899 
                 split hand/foot malformation (ectrodactyly) type 1 
                 DNA Damage Repair 
               
               
                 SKP2 
                 6502 
                 NM_005983 
                 S-phase kinase-associated protein 2 (p45) 
                 Cell Cycle 
               
               
                 SMARCA4 
                 6597 
                 NM_003072 
                 SWI/SNF related, matrix associated, actin dependent 
                 DNA Damage Repair 
               
               
                   
                   
                   
                 regulator of chromatin, subfamily a, member 4 
               
               
                 SMUG1 
                 23583 
                 AK091468 
                 single-strand-selective monofunctional uracil-DNA glycosylase 1 
                 DNA Damage Repair 
               
               
                 SND1 
                 27044 
                 NM_014390 
                 staphylococcal nuclease and tudor domain containing 1 
                 DNA Damage Repair 
               
               
                 SNRPE 
                 6635 
                 In multiple clusters 
                 small nuclear ribonucleoprotein polypeptide E 
                 DNA Damage Repair 
               
               
                 SNRPF 
                 6636 
                 CD388516 
                 small nuclear ribonucleoprotein polypeptide F 
                 DNA Damage Repair 
               
               
                 SOD1 
                 6647 
                 NM_000454 
                 Superoxide dismutase 1, soluble (amyotrophic lateral 
                 Drug Resistance 
               
               
                   
                   
                   
                 sclerosis 1 (adult)) 
               
               
                 SOX4 
                 6659 
                 NM_003107 
                 SRY (sex determining region Y)-box 4 
                 DNA Damage Repair 
               
               
                 SPO11 
                 23626 
                 AF1 69385 
                 SPO11 meiotic protein covalently bound to DSB homolog 
                 DNA Damage Repair 
               
               
                   
                   
                   
                 ( S. cerevisiae ) 
               
               
                 SSBP1 
                 6742 
                 BC008402 
                 single-stranded DNA binding protein 1 
                 DNA Damage Repair 
               
               
                 SSR1 
                 6745 
                 NM_003144 
                 signal sequence receptor, alpha (translocon-associated protein 
                 DNA Damage Repair 
               
               
                   
                   
                   
                 alpha) 
               
               
                 STAT1 
                 6772 
                 NM_007315 
                 Signal transducer and activator of transcription 1, 91 kDa 
                 p53 Pathway 
               
               
                 SULT1E1 
                 6783 
                 NM_005420 
                 Sulfotransferase family 1E, estrogen-preferring, member 1 
                 Drug Resistance 
               
               
                 SUMO1 
                 7341 
                 NM_003352 
                 SMT3 suppressor of mif two 3 homolog 1 ( S. cerevisiae ) 
                 Cell Cycle 
               
               
                 TAP1 
                 6890 
                 NM_000593 
                 Transporter 1, ATP-binding cassette, sub-family B (MDR/TAP) 
                 Drug Transporters 
               
               
                 TAP2 
                 6891 
                 NM_000544 
                 Transporter 2, ATP-binding cassette, sub-family B (MDR/TAP) 
                 Drug Transporters 
               
               
                 TARS 
                 6897 
                 NM_152295 
                 threonyl-tRNA synthetase 
                 DNA Damage Repair 
               
               
                 TDG 
                 6996 
                 NM_003211 
                 thymine-DNA glycosylase 
                 DNA Damage Repair 
               
               
                 TDP1 
                 55775 
                 NM_018319 
                 tyrosyl-DNA phosphodiesterase 1 
                 DNA Damage Repair 
               
               
                 TFDP1 
                 7027 
                 NM_007111 
                 Transcription factor Dp-1 
                 Cell Cycle 
               
               
                 TFDP2 
                 7029 
                 NM_006286 
                 Transcription factor Dp-2 (E2F dimerization partner 2) 
                 Cell Cycle 
               
               
                 TGIF1 
                 7050 
                 NM_170695 
                 TGFB-induced factor homeobox 1 
                 DNA Damage Repair 
               
               
                 TMEM30A 
                 55754 
                 NM_018247 
                 transmembrane protein 30A 
                 DNA Damage Repair 
               
               
                 TNF 
                 7124 
                 NM_000594 
                 Tumor necrosis factor (TNF superfamily, member 2) 
                 Apoptosis 
               
               
                 TNFRSF10A 
                 8797 
                 NM_003844 
                 Tumor necrosis factor receptor superfamily, member 10a 
                 Apoptosis 
               
               
                 TNFRSF10B 
                 8795 
                 NM_003842 
                 Tumor necrosis factor receptor superfamily, member 10b 
                 Apoptosis 
               
               
                 TNFRSF10D 
                 8793 
                 NM_003840 
                 Tumor necrosis factor receptor superfamily, member 10d, 
                 p53 Pathway 
               
               
                   
                   
                   
                 decoy with truncated death domain 
               
               
                 TNFRSF11A 
                 8792 
                 NM_003839 
                 Tumor necrosis factor receptor superfamily, member 11a, 
                 Drug Resistance 
               
               
                   
                   
                   
                 NFKB activator 
               
               
                 TNFRSF11B 
                 4982 
                 NM_002546 
                 Tumor necrosis factor receptor superfamily, member 11b 
                 Apoptosis 
               
               
                   
                   
                   
                 (osteoprotegerin) 
               
               
                 TNFRSF1A 
                 7132 
                 NM_001065 
                 Tumor necrosis factor receptor superfamily, member 1A 
                 Apoptosis 
               
               
                 TNFRSF21 
                 27242 
                 NM_014452 
                 Tumor necrosis factor receptor superfamily, member 21 
                 Apoptosis 
               
               
                 TNFRSF25 
                 8718 
                 NM_003790 
                 Tumor necrosis factor receptor superfamily, member 25 
                 Apoptosis 
               
               
                 TNFRSF9 
                 3604 
                 NM_001561 
                 Tumor necrosis factor receptor superfamily, member 9 
                 Apoptosis 
               
               
                 TNFSF10 
                 8743 
                 NM_003810 
                 Tumor necrosis factor (ligand) superfamily, member 10 
                 Apoptosis 
               
               
                 TNFSF8 
                 944 
                 NM_001244 
                 Tumor necrosis factor (ligand) superfamily, member 8 
                 Apoptosis 
               
               
                 TOP1 
                 7150 
                 NM_003286 
                 Topoisomerase (DNA) I 
                 Drug Resistance 
               
               
                 TOP2A 
                 7153 
                 NM_001067 
                 Topoisomerase (DNA) II alpha 170kDa 
                 Drug Resistance 
               
               
                 TOP2B 
                 7155 
                 NM_001068 
                 Topoisomerase (DNA) II beta 180kDa 
                 Drug Resistance 
               
               
                 TP53 
                 7157 
                 NM_000546 
                 Tumor protein p53 
                 p53 Pathway 
               
               
                 TP53 
                 7157 
                 NM_000546 
                 Tumor protein p53 
                 p53 Pathway 
               
               
                 TP53BP1 
                 7158 
                 AF078776 
                 tumor protein p53 binding protein, 1 
                 DNA Damage Repair 
               
               
                 TP53BP2 
                 7159 
                 NM_005426 
                 Tumor protein p53 binding protein, 2 
                 Apoptosis 
               
               
                 TP63 
                 8626 
                 NM_003722 
                 Tumor protein p63 
                 p53 Pathway 
               
               
                 TP73 
                 7161 
                 NM_005427 
                 Tumor protein p73 
                 Apoptosis 
               
               
                 TPMT 
                 7172 
                 NM_000367 
                 Thiopurine S-methyltransferase 
                 Drug Resistance 
               
               
                 TPX2 
                 22974 
                 NM_012112 
                 TPX2, microtubule-associated, homolog ( Xenopus laevis ) 
                 DNA Damage Repair 
               
               
                 TRADD 
                 8717 
                 NM_003789 
                 TNFRSF1A-associated via death domain 
                 Apoptosis 
               
               
                 TRAF2 
                 7186 
                 NM_021138 
                 TNF receptor-associated factor 2 
                 Apoptosis 
               
               
                 TRAF3 
                 7187 
                 NM_003300 
                 TNF receptor-associated factor 3 
                 Apoptosis 
               
               
                 TRAF4 
                 9618 
                 NM_004295 
                 TNF receptor-associated factor 4 
                 Apoptosis 
               
               
                 TRDMT1 
                 1787 
                 BX537961 
                 tRNA aspartic acid methyltransferase 1 
                 DNA Damage Repair 
               
               
                 TREX1 
                 11277 
                 In multiple clusters 
                 three prime repair exonuclease 1 
                 DNA Damage Repair 
               
               
                 TREX2 
                 11219 
                 NM_080701 
                 three prime repair exonuclease 2 
                 DNA Damage Repair 
               
               
                 TSTA3 
                 7264 
                 AK096752 
                 tissue specific transplantation antigen P35B 
                 DNA Damage Repair 
               
               
                 TUBB 
                 203068 
                 In multiple clusters 
                 tubulin, beta 
                 DNA Damage Repair 
               
               
                 UBA1 
                 7317 
                 NM_003334 
                 Ubiquitin-like modifier activating enzyme 1 
                 Cell Cycle 
               
               
                 UBE2A 
                 7319 
                 BC042021 
                 ubiquitin-conjugating enzyme E2A (RAD6 homolog) 
                 DNA Damage Repair 
               
               
                 UBE2B 
                 7320 
                 In multiple clusters 
                 ubiquitin-conjugating enzyme E2B (RAD6 homolog) 
                 DNA Damage Repair 
               
               
                 UBE2N 
                 7334 
                 NM_003348 
                 ubiquitin-conjugating enzyme E2N (UBC13 homolog, yeast) 
                 DNA Damage Repair 
               
               
                 UBE2S 
                 27338 
                 BM479313 
                 ubiquitin-conjugating enzyme E2S 
                 DNA Damage Repair 
               
               
                 UBE2V2 
                 7336 
                 AK094617 
                 ubiquitin-conjugating enzyme E2 variant 2 
                 DNA Damage Repair 
               
               
                 UNG 
                 7374 
                 NM_003362 
                 uracil-DNA glycosylase 
                 DNA Damage Repair 
               
               
                 VDAC1 
                 7416 
                 NM_003374 
                 Voltage-dependent anion channel 1 
                 Drug Transporters 
               
               
                 VDAC2 
                 7417 
                 NM_003375 
                 Voltage-dependent anion channel 2 
                 Drug Transporters 
               
               
                 XAB2 
                 56949 
                 AK074035 
                 XPA binding protein 2 
                 DNA Damage Repair 
               
               
                 XIAP 
                 331 
                 NM_001167 
                 X-linked inhibitor of apoptosis 
                 Apoptosis 
               
               
                 XPA 
                 7507 
                 AK021661 
                 xeroderma pigmentosum, complementation group A 
                 NER 
               
               
                 XPC 
                 7508 
                 NM_004628 
                 xeroderma pigmentosum, complementation group C 
                 NER 
               
               
                 XRCC1 
                 7515 
                 CR591751 
                 X-ray repair complementing defective repair in 
                 DNA Damage Repair 
               
               
                   
                   
                   
                 Chinese hamster cells 1 
               
               
                 XRCC2 
                 7516 
                 CR749256 
                 X-ray repair complementing defective repair in 
                 DNA Damage Repair 
               
               
                   
                   
                   
                 Chinese hamster cells 2 
               
               
                 XRCC3 
                 7517 
                 AK124498 
                 X-ray repair complementing defective repair in 
                 DNA Damage Repair 
               
               
                   
                   
                   
                 Chinese hamster cells 3 
               
               
                 XRCC4 
                 7518 
                 NM_022550 
                 X-ray repair complementing defective repair in 
                 DNA Damage Repair 
               
               
                   
                   
                   
                 Chinese hamster cells 4 
               
               
                 XRCC5 
                 7520 
                 NM_021141 
                 X-ray repair complementing defective repair in 
                 p53 Pathway 
               
               
                   
                   
                   
                 Chinese hamster cells 5 (double-strand-break 
               
               
                   
                   
                   
                 rejoining; Ku autoantigen, 80 kDa) 
               
               
                 XRCC6 
                 2547 
                 BC008343 
                 X-ray repair complementing defective repair in 
                 DNA Damage Repair 
               
               
                   
                   
                   
                 Chinese hamster cells 6 (Ku autoantigen, 70 kDa) 
               
               
                 ZDHHC17 
                 23390 
                 AB024494 
                 zinc finger, DHHC-type containing 17 
                 DNA Damage Repair 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 2 
               
               
                   
               
             
            
               
                   
                   
                   
                 Median Fold 
                   
               
               
                   
                   
                   
                 Change IC50 
                   
               
               
                   
                 Entrez 
                   
                 Oxaliplatin 
                   
               
               
                 Symbol 
                 ID 
                 Description 
                 (Log 2 ) 
                 RSA P-value 
               
               
                   
               
               
                 ATP6V0C 
                 527 
                 ATPase, H+ transporting, lysosomal 16 kDa,V0 subunit c 
                 0.57 
                 3.08E−02 
               
               
                   
               
               
                 BCL10 
                 8915 
                 B-cell CLL/lymphoma 10 
                 0.65 
                 4.76E−03 
               
               
                   
               
               
                 BCL2L10 
                 10017 
                 BCL2-like 10 (apoptosis facilitator) 
                 0.85 
                 1.03E−03 
               
               
                   
               
               
                 BFAR 
                 51283 
                 bifunctional apoptosis regulator 
                 0.86 
                 7.85E−04 
               
               
                   
               
               
                 BRIP1 
                 10549 
                 BRCA1 interacting protein C-terminal helicase 1 
                 0.72 
                 1.65E−03 
               
               
                   
               
               
                 CARD6 
                 84674 
                 caspase recruitment domain family, member 6 
                 0.86 
                 9.33E−04 
               
               
                   
               
               
                 CCND1 
                 595 
                 cyclin D1 
                 0.61 
                 6.18E−04 
               
               
                   
               
               
                 CDC20 
                 991 
                 cell division cycle 20 homolog ( S .  cerevisiae ) 
                 0.70 
                 6.74E−03 
               
               
                   
               
               
                 CDC25A 
                 993 
                 cell division cycle 25 homolog A ( S .  pombe ) 
                 0.56 
                 1.93E−02 
               
               
                   
               
               
                 CFLAR 
                 8837 
                 CASP8 and FADD-like apoptosis regulator 
                 0.62 
                 1.56E−02 
               
               
                   
               
               
                 CHAF1A 
                 10036 
                 chromatin assembly factor 1, subunit A (p150) 
                 0.68 
                 2.67E−03 
               
               
                   
               
               
                 CRADD 
                 8738 
                 CASP2 and RIPK1 domain containing adaptor with death domain 
                 0.71 
                 1.11E−02 
               
               
                   
               
               
                 CUL4B 
                 8450 
                 cullin 4B 
                 0.74 
                 1.59E−03 
               
               
                   
               
               
                 DFFA 
                 1676 
                 DNA fragmentation factor, 45 kDa, alpha polypeptide 
                 0.74 
                 1.31E−03 
               
               
                   
               
               
                 E2F2 
                 1870 
                 E2F transcription factor 2 
                 0.59 
                 2.35E−02 
               
               
                   
               
               
                 E2F4 
                 1874 
                 E2F transcription factor 4, p107/p130-binding 
                 0.60 
                 3.98E−02 
               
               
                   
               
               
                 E2F6 
                 1876 
                 E2F transcription factor 6 
                 0.75 
                 1.08E−02 
               
               
                   
               
               
                 GADD45B 
                 4616 
                 growth arrest and DNA-damage-inducible, beta 
                 0.83 
                 1.85E−02 
               
               
                   
               
               
                 HMG20B 
                 10362 
                 high-mobility group 20B 
                 1.08 
                 1.46E−02 
               
               
                   
               
               
                 IL8 
                 3576 
                 interleukin 8 
                 0.80 
                 1.23E−03 
               
               
                   
               
               
                 LTBR 
                 4055 
                 lymphotoxin beta receptor (TNFR superfamily, member 3) 
                 1.56 
                 7.65E−05 
               
               
                   
               
               
                 MBD2 
                 8932 
                 methyl-CpG binding domain protein 2 
                 0.74 
                 1.52E−03 
               
               
                   
               
               
                 MBD3 
                 53615 
                 methyl-CpG binding domain protein 3 
                 0.56 
                 3.78E−02 
               
               
                   
               
               
                 MBD4 
                 8930 
                 methyl-CpG binding domain protein 4 
                 1.10 
                 3.01E−04 
               
               
                   
               
               
                 MCM3 
                 4172 
                 minichromosome maintenance complex component 3 
                 1.17 
                 1.31E−04 
               
               
                   
               
               
                 MCM4 
                 4173 
                 minichromosome maintenance complex component 4 
                 0.62 
                 4.80E−03 
               
               
                   
               
               
                 MCM6 
                 4175 
                 minichromosome maintenance complex component 6 
                 0.66 
                 3.08E−03 
               
               
                   
               
               
                 MGST3 
                 4259 
                 microsomal glutathione S-transferase 3 
                 0.58 
                 8.03E−03 
               
               
                   
               
               
                 MPG 
                 4350 
                 N-methylpurine-DNA glycosylase 
                 0.99 
                 6.72E−04 
               
               
                   
               
               
                 MRPL3 
                 11222 
                 mitochondrial ribosomal protein L3 
                 0.53 
                 9.89E−03 
               
               
                   
               
               
                 MSH4 
                 4438 
                 mutS homolog 4 ( E .  coli ) 
                 0.66 
                 2.75E−03 
               
               
                   
               
               
                 NHEJ1 
                 79840 
                 nonhomologous end-joining factor 1 
                 1.09 
                 4.09E−04 
               
               
                   
               
               
                 OGT 
                 8473 
                 O-linked N-acetylglucosamine (GlcNAc) transferase (UDP-N- 
                 0.55 
                 7.73E−04 
               
               
                   
                   
                 acetylglucosamine:pol   
                   
                   
               
               
                   
               
               
                 PAICS 
                 10606 
                 phosphoribosylaminoimidazole carboxylase, phosphoribo- 
                 0.51 
                 3.40E−02 
               
               
                   
                   
                 sylaminoimidazole succi    
                   
                   
               
               
                   
               
               
                 PPP2R5C 
                 5527 
                 protein phosphatase 2, regulatory subunit B′, gamma 
                 0.60 
                 1.14E−03 
               
               
                   
               
               
                 PRDX4 
                 10549 
                 peroxiredoxin 4 
                 0.64 
                 4.77E−03 
               
               
                   
               
               
                 PTTG1 
                 9232 
                 pituitary tumor-transforming 1 
                 0.83 
                 1.06E−03 
               
               
                   
               
               
                 RAD51L1 
                 5890 
                 RAD51-like 1 ( S .  cerevisiae ) 
                 0.87 
                 7.56E−04 
               
               
                   
               
               
                 RARA 
                 5914 
                 retinoic acid receptor, alpha 
                 0.64 
                 1.19E−02 
               
               
                   
               
               
                 RBM4 
                 5936 
                 RNA binding motif protein 4 
                 0.70 
                 2.00E−02 
               
               
                   
               
               
                 RECQL 
                 5965 
                 RecQ protein-like (DNA helicase Q1-like) 
                 0.56 
                 5.88E−04 
               
               
                   
               
               
                 RRM1 
                 6240 
                 ribonucleotide reductase M1 
                 0.76 
                 1.28E−03 
               
               
                   
               
               
                 SHFM1 
                 8930 
                 split hand/foot malformation (ectrodactyly) type 1 
                 1.11 
                 1.50E−04 
               
               
                   
               
               
                 SP011 
                 23626 
                 SPO11 meiotic protein covalently bound to DSB homolog 
                 0.70 
                 2.53E−02 
               
               
                   
                   
                 ( S .  cerevisiae ) 
                   
                   
               
               
                   
               
               
                 TMEM30A 
                 55754 
                 transmembrane protein 30A 
                 1.49 
                 9.85E−05 
               
               
                   
               
               
                 UBE2A 
                 7319 
                 ubiquitin-conjugating enzyme E2A (RAD6 homolog) 
                 0.53 
                 2.26E−04 
               
               
                   
               
               
                 UBE2S 
                 27338 
                 ubiquitin-conjugating enzyme E2S 
                 0.50 
                 4.83E−02 
               
               
                   
               
               
                 XAB2 
                 56949 
                 XPA binding protein 2 
                 0.74 
                 4.77E−02 
               
               
                   
               
               
                 XRCC2 
                 7516 
                 X-ray repair complementing defective repair in Chinese 
                 0.81 
                 5.54E−03 
               
               
                   
                   
                 hamster cells 2 
               
               
                   
               
               
                   
                   
                   
                 Median Fold 
                   
               
               
                   
                   
                   
                 Change IC50 
                   
               
               
                   
                   
                   
                 Oxaliplatin 
                   
               
               
                   
                 Entrez 
                   
                 (Log 2 ) 
                   
               
               
                 Symbol 
                 ID 
                 Description 
                 from HTS 
                 RSA P-value 
               
               
                   
               
               
                 ABL1 
                 25 
                 c-abl oncogene 1, receptor tyrosine kinase 
                 −0.33 
                 2.51E−02 
               
               
                   
               
               
                 APAF1 
                 317 
                 apoptotic peptidase activating factor 1 
                 −0.34 
                 4.61E−02 
               
               
                   
               
               
                 BAX 
                 581 
                 BCL2-associated X protein 
                 −0.42 
                 7.92E−03 
               
               
                   
               
               
                 CARD4 
                 10392 
                 nucleotide-binding oligomerization domain containing 1 
                 −0.44 
                 1.63E−03 
               
               
                   
               
               
                 CASP5 
                 838 
                 caspase 5, apoptosis-related cysteine peptidase 
                 −0.36 
                 1.00E−02 
               
               
                   
               
               
                 CCT5 
                 22948 
                 chaperonin containing TCP1, subunit 5 (epsilon) 
                 −0.49 
                 4.28E−04 
               
               
                   
               
               
                 CDKN1A 
                 1026 
                 cyclin-dependent kinase inhibitor 1A (p21, Cip1) 
                 −1.51 
                 1.02E−13 
               
               
                   
               
               
                 CDKN3 
                 1033 
                 cyclin-dependent kinase inhibitor 3 
                 −0.30 
                 1.21E−02 
               
               
                   
               
               
                 CIDEA 
                 1149 
                 cell death-inducing DFFA-like effector a 
                 −0.35 
                 6.90E−04 
               
               
                   
               
               
                 CRIP2 
                 1397 
                 cysteine-rich protein 2 
                 −0.38 
                 5.90E−03 
               
               
                   
               
               
                 CUL1 
                 8454 
                 cullin 1 
                 −0.39 
                 8.05E−03 
               
               
                   
               
               
                 CYP1A2 
                 1544 
                 cytochrome P450, family 1, subfamily A, polypeptide 2 
                 −0.29 
                 2.12E−03 
               
               
                   
               
               
                 DNMT1 
                 1786 
                 DNA (cytosine-5-)-methyltransferase 1 
                 −0.45 
                 1.88E−04 
               
               
                   
               
               
                 ERCC4 
                 2072 
                 excision repair cross-complementing rodent repair 
                 −0.37 
                 1.61E−03 
               
               
                   
                   
                 deficiency, complementation g   
                   
                   
               
               
                   
               
               
                 FANCE 
                 2178 
                 Fanconi anemia, complementation group E 
                 −0.56 
                 2.56E−02 
               
               
                   
               
               
                 GSTT1 
                 2952 
                 glutathione S-transferase theta 1 
                 −0.44 
                 4.10E−02 
               
               
                   
               
               
                 GSTZ1 
                 2954 
                 glutathione transferase zeta 1 
                 −0.35 
                 1.13E−02 
               
               
                   
               
               
                 GTF2H5 
                 404672 
                 general transcription factor IIH, polypeptide 5 
                 −0.31 
                 3.70E−02 
               
               
                   
               
               
                 KPNA2 
                 3838 
                 karyopherin alpha 2 (RAG cohort 1, importin alpha 1) 
                 −0.55 
                 5.34E−04 
               
               
                   
               
               
                 MRPS12 
                 6183 
                 mitochondrial ribosomal protein S12 
                 −0.28 
                 2.40E−03 
               
               
                   
               
               
                 MSH5 
                 4439 
                 mutS homolog 5 ( E .  coli ) 
                 −0.72 
                 1.10E−02 
               
               
                   
               
               
                 NFKB1 
                 4790 
                 nuclear factor of kappa light polypeptide gene enhancer 
                 −0.41 
                 5.12E−04 
               
               
                   
                   
                 in B-cells 1 
                   
                   
               
               
                   
               
               
                 PTEN 
                 5728 
                 phosphatase and tensin homolog 
                 −0.35 
                 3.62E−04 
               
               
                   
               
               
                 SMARCA4 
                 6597 
                 SWI/SNF related, matrix associated, actin dependent 
                 −0.29 
                 1.66E−02 
               
               
                   
                   
                 regulator of chromatin, subfa   
                   
                   
               
               
                   
               
               
                 SND1 
                 27044 
                 staphylococcal nuclease and tudor domain containing 1 
                 −0.31 
                 3.87E−03 
               
               
                   
               
               
                 SOX4 
                 6659 
                 SRY (sex determining region Y)-box 4 
                 −0.45 
                 5.23E−04 
               
               
                   
               
               
                 SUMO1 
                 7341 
                 SMT3 suppressor of mif two 3 homolog 1 ( S .  cerevisiae ) 
                 −0.58 
                 2.01E−05 
               
               
                   
               
               
                 TARS 
                 6897 
                 threonyl-tRNA synthetase 
                 −0.37 
                 1.19E−02 
               
               
                   
               
               
                 TNFRSF10A 
                 8797 
                 tumor necrosis factor receptor superfamily, member 10a 
                 −0.38 
                 7.99E−03 
               
               
                   
               
               
                 TNFSF8 
                 944 
                 tumor necrosis factor (ligand) superfamily, member 8 
                 −0.36 
                 1.68E−02 
               
               
                   
               
               
                 TP53 
                 7157 
                 tumor protein p53 
                 −1.51 
                 2.27E−05 
               
               
                   
               
               
                 XPC 
                 7508 
                 xeroderma pigmentosum, complementation group C 
                 −0.43 
                 4.42E−04 
               
               
                   
               
               
                 XRCC3 
                 7517 
                 X-ray repair complementing defective repair in Chinese 
                 −0.38 
                 2.12E−03 
               
               
                   
                   
                 hamster cells 3 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                   
                 SEQ 
                   
                 SEQ 
                   
                 SEQ 
                   
                 SEQ 
                   
               
               
                   
                 ID 
                 siRNA Sequence 1 
                 ID 
                 siNA Sequence 2 
                 ID 
                 siRNA Sequence 3 
                 ID 
                 siRNA Sequence 4 
               
               
                 Symbol 
                 NO. 
                 from HTS 
                 NO. 
                 from HTS 
                 NO. 
                 from HTS 
                 NO. 
                 from HTS 
               
               
                   
               
               
                 ATP6V0C 
                 1 
                 CAGCCACAGAATATT 
                 2 
                 CTGGATGTTTATTTA 
                 3 
                 TAGAATTGTCATTTC 
                 4 
                 TCCCAGCTATCTATA 
               
               
                   
                   
                 ATGTAA 
                   
                 TAAAGA 
                   
                 TCTTTA 
                   
                 ACCTTA 
               
               
                   
               
               
                 BCL10 
                 5 
                 CACGTACTGTTTCAC 
                 6 
                 GTGCTGAAACTTAGA 
                 7 
                 AGGGAATATATCTCT 
                 8 
                 ACACAGCGCCATAGT 
               
               
                   
                   
                 GACAAT 
                   
                 AATATA 
                   
                 ATTTGA 
                   
                 AGTTAA 
               
               
                   
               
               
                 BCL2L10 
                 9 
                 ACAGATGTGTGAGAA 
                 10 
                 ATGACAGATGTGTGA 
                 11 
                 ATGGCTCTTCCTTGA 
                 12 
                 CTGCCCAACTGTGAC 
               
               
                   
                   
                 CAAGAA 
                   
                 GAACAA 
                   
                 GTGAAA 
                   
                 CAACTA 
               
               
                   
               
               
                 BFAR 
                 13 
                 CCGGGACGAGTGGAA 
                 14 
                 TCCGGTGTGCTCACA 
                 15 
                 CAGGTCCCTGTTCCT 
                 16 
                 CGGGACGAGTGGAAT 
               
               
                   
                   
                 TGATTA 
                   
                 GCTTTA 
                   
                 GCTATA 
                   
                 GATTAA 
               
               
                   
               
               
                 BRIP1 
                 17 
                 CCTGAACTTTACGAT 
                 18 
                 AAGATAAACAGTCCA 
                 19 
                 CAGGCCCTTGGTAGA 
                 20 
                 TAGCATGGCAACAAT 
               
               
                   
                   
                 CCTGAA 
                   
                 CTTCAA 
                   
                 TGTATT 
                   
                 CTCTTA 
               
               
                   
               
               
                 CARD6 
                 21 
                 AACCTTCTCCATGCA 
                 22 
                 CCCAATTTGCTTGAA 
                 23 
                 CTGCTTATTTGGTGT 
                 24 
                 AAGTGTTATATCCCT 
               
               
                   
                   
                 AATCTA 
                   
                 TGGGAA 
                   
                 GGTTAA 
                   
                 AACCAA 
               
               
                   
               
               
                 CCND1 
                 25 
                 AAGGCCAGTATGATT 
                 26 
                 CTCCTACGATACGCT 
                 27 
                 AGGGTTATCTTAGAT 
                 28 
                 ATGCATGTAGTCACT 
               
               
                   
                   
                 TATAAA 
                   
                 ACTATA 
                   
                 GTTTCA 
                   
                 TTATAA 
               
               
                   
               
               
                 CDC20 
                 29 
                 CACCACCATGATGTT 
                 30 
                 CTCCCTAAGCTGGAA 
                 31 
                 AAGGCATCCGCTGAA 
                 32 
                 CAGACATTCACCCAG 
               
               
                   
                   
                 CGGGTA 
                   
                 CAGCTA 
                   
                 GACCAA 
                   
                 CATCAA 
               
               
                   
               
               
                 CDC25A 
                 33 
                 AAGGCGCTATTTGGC 
                 34 
                 AAGGGTTATCTCTTT 
                 35 
                 CAGCTTAGCTAGCAT 
                 36 
                 CTGGCCAAATAGCAA 
               
               
                   
                   
                 GCTTCA 
                   
                 CATACA 
                   
                 TACTAA 
                   
                 AGACAA 
               
               
                   
               
               
                 CFLAR 
                 37 
                 CACCGACGAGTCTCA 
                 38 
                 TCGAGGCATTACAAT 
                 39 
                 TTGCCTCAGAGCATA 
                 40 
                 CACCTTGTTTCGGAC 
               
               
                   
                   
                 ACTAAA 
                   
                 CGCGAA 
                   
                 CCTGAA 
                   
                 TATAGA 
               
               
                   
               
               
                 CHAF1A 
                 41 
                 CACAATAAACTAAAT 
                 42 
                 AAGGAAGAAGAGAAA 
                 43 
                 CTGCCCTTTAATAAA 
                 44 
                 CAGCCATGGATTGCA 
               
               
                   
                   
                 TCTGAA 
                   
                 CGGTTA 
                   
                 GCATTA 
                   
                 AAGATA 
               
               
                   
               
               
                 CRADD 
                 45 
                 AGGCAGGTGTCTCAT 
                 46 
                 CAGGGTTTCCACTAG 
                 47 
                 ATGCGAATTACTATA 
                 48 
                 AATGCGAATTACTAT 
               
               
                   
                   
                 ATGTAA 
                   
                 ACATTA 
                   
                 TATAAT 
                   
                 ATATAA 
               
               
                   
               
               
                 CUL4B 
                 49 
                 AAGGTGTTAAATACA 
                 50 
                 AATGATGATTTCAAA 
                 51 
                 AAAGATAAGGTTGAC 
                 52 
                 TGGCAGCACTATTGT 
               
               
                   
                   
                 CATGAA 
                   
                 CATAAA 
                   
                 CATATA 
                   
                 AATTAA 
               
               
                   
               
               
                 DFFA 
                 53 
                 CCGGAGCATCTCAGC 
                 54 
                 TGCCTTGAACTGGGA 
                 55 
                 CTGGCAGAGGATGGC 
                 56 
                 CAGCATCATCCTCCT 
               
               
                   
                   
                 AAGCAA 
                   
                 CATAAA 
                   
                 ACCATA 
                   
                 ATCAGA 
               
               
                   
               
               
                 E2F2 
                 57 
                 TTGAGACGAGGGATT 
                 58 
                 TAGGGACCAGGTAGA 
                 59 
                 ACCCATTGGGAATGA 
                 60 
                 TCCGTGCTGTTGGCA 
               
               
                   
                   
                 ATTTCA 
                   
                 CTTTAA 
                   
                 GTTTAA 
                   
                 ACTTTA 
               
               
                   
               
               
                 E2F4 
                 61 
                 AGGTATCGGGCTAAT 
                 62 
                 AACGAATGGATTCCT 
                 63 
                 ACCCGGGAGATTGCT 
                 64 
                 GCGGATTTACGACAT 
               
               
                   
                   
                 CGAGAA 
                   
                 ATATAA 
                   
                 GACAAA 
                   
                 TACCAA 
               
               
                   
               
               
                 E2F6 
                 65 
                 CAGGGTCAGACCAGT 
                 66 
                 CAGGAGGAACTTTCT 
                 67 
                 CAGATCGTCATTGCA 
                 68 
                 ACCACTTAGATTACT 
               
               
                   
                   
                 AACAAA 
                   
                 GACTTA 
                   
                 GTTAAA 
                   
                 GAGTAA 
               
               
                   
               
               
                 GADD45B 
                 69 
                 GAGGATGACATCGCC 
                 70 
                 TCCCAGTTTGCGAAT 
                 71 
                 TCGTTGGAGACTGAA 
                 72 
                 CTGCTGTGACAACGA 
               
               
                   
                   
                 CTGCAA 
                   
                 TAATAA 
                   
                 GAGAAA 
                   
                 CATCAA 
               
               
                   
               
               
                 HMG20B 
                 73 
                 CAGCATCCCTTTAGC 
                 74 
                 TCGGCGCTTGCGGAA 
                 75 
                 CCAGGAGAAGAAGAT 
                 76 
                 CACGGAGAAGATCCA 
               
               
                   
                   
                 TTTCAA 
                   
                 GATGAA 
                   
                 CAAGAA 
                   
                 GGAGAA 
               
               
                   
               
               
                 IL8 
                 77 
                 AACAATTGGGTACCC 
                 78 
                 CTGCGCCAACACAGA 
                 79 
                 CTGATTGTATGGAAA 
                 80 
                 CTGGTTGAAACTTGT 
               
               
                   
                   
                 AGTTAA 
                   
                 AATTAT 
                   
                 TATAAA 
                   
                 TTATTA 
               
               
                   
               
               
                 LTBR 
                 81 
                 CCGCCACACGGTCAC 
                 82 
                 CCGGCGGGTCTATGA 
                 83 
                 AAAGGGAGTCATTAA 
                 84 
                 TACATCTACAATGGA 
               
               
                   
                   
                 CTGCAA 
                   
                 CTATCA 
                   
                 CAACTA 
                   
                 CCAGTA 
               
               
                   
               
               
                 MBD2 
                 85 
                 AAGATGATGCCTAGT 
                 86 
                 TGGAAAGATGATGCC 
                 87 
                 CTCGCGAGTGTAACT 
                 88 
                 ACCCTTCAGGTGTTA 
               
               
                   
                   
                 AAATTA 
                   
                 TAGTAA 
                   
                 TTCATA 
                   
                 CTAGAA 
               
               
                   
               
               
                 MBD3 
                 89 
                 CCCGGAGATGGAGCA 
                 90 
                 GCCGGTGACCAAGAT 
                 91 
                 CCAGACGGCGTCCAT 
                 92 
                 CGGGAAGAAGTTCCG 
               
               
                   
                   
                 CGTCTA 
                   
                 TACCAA 
                   
                 CTTCAA 
                   
                 CAGCAA 
               
               
                   
               
               
                 MBD4 
                 93 
                 AAGCTTCTCATCGCT 
                 94 
                 CCGCCGAATGACCTC 
                 95 
                 AAGAGAATCTGTGTG 
                 96 
                 CCGAATGACCTCCGC 
               
               
                   
                   
                 ACTATA 
                   
                 CGCAAA 
                   
                 TAATAA 
                   
                 AAAGAA 
               
               
                   
               
               
                 MCM3 
                 97 
                 CACGATTTGACTTGC 
                 98 
                 CGGCAGGTATGACCA 
                 99 
                 ATCCAGGTTGAAGGC 
                 100 
                 CAGGGAATTTATCAG 
               
               
                   
                   
                 TCTTCA 
                   
                 GTATAA 
                   
                 ATTCAA 
                   
                 AGCAAA 
               
               
                   
               
               
                 MCM4 
                 101 
                 CACATTGATGTCATT 
                 102 
                 CTCGACAGCTAGAGT 
                 103 
                 CTGCATGGCCTTGAT 
                 104 
                 CCAAGCATTTATGAA 
               
               
                   
                   
                 CATTAT 
                   
                 CATTAA 
                   
                 GAAGAA 
                   
                 CATGAA 
               
               
                   
               
               
                 MCM6 
                 105 
                 CTGGAACAATTTAAC 
                 106 
                 TACAATGAAGACATA 
                 107 
                 CCCAGTGAAGTTGGA 
                 108 
                 TCCGGTTACTGAATA 
               
               
                   
                   
                 CAGCAA 
                   
                 AATCAA 
                   
                 ACCAAA 
                   
                 AATCAA 
               
               
                   
               
               
                 MGST3 
                 109 
                 CCAGAACACGTTGGA 
                 110 
                 CTGGTGCTGCCAGCT 
                 111 
                 ATGGCTGTCCTCTCT 
                 112 
                 CAAGATGGCTGTCCT 
               
               
                   
                   
                 AGTGTA 
                   
                 TTATAA 
                   
                 AAGGAA 
                   
                 CTCTAA 
               
               
                   
               
               
                 MPG 
                 113 
                 CAACCGAGGCATGTT 
                 114 
                 CAGGGTGTTTGTGCC 
                 115 
                 CTGGCACAGGATGAA 
                 116 
                 CCCGCTTTGCAGATG 
               
               
                   
                   
                 CATGAA 
                   
                 TCATAA 
                   
                 GCTGTA 
                   
                 AAGAAA 
               
               
                   
               
               
                 MRPL3 
                 117 
                 CACATTAAATATATG 
                 118 
                 CCGCCGAAACAGACA 
                 119 
                 AGGGCATAAATATAT 
                 120 
                 GCCGCCGAAACAGAC 
               
               
                   
                   
                 AGTTAA 
                   
                 GTTAAA 
                   
                 CATTCA 
                   
                 AGTTAA 
               
               
                   
               
               
                 MSH4 
                 121 
                 ATGCAGTGAGGTCTA 
                 122 
                 TCGCTCATATTAATT 
                 123 
                 ATCAATTGTCTTGGA 
                 124 
                 AACCATTAACATGAG 
               
               
                   
                   
                 ACATAA 
                   
                 GATGAA 
                   
                 TGCCAA 
                   
                 ATTAGA 
               
               
                   
               
               
                 NHEJ1 
                 125 
                 CTGGAGATCCTCATA 
                 126 
                 CTGCAAGGAATCGAT 
                 127 
                 CCGCCTCATCCTTCT 
                 128 
                 GAGAAGATGATCAAA 
               
               
                   
                   
                 CCTCAA 
                   
                 AGCCAA 
                   
                 GCATAA 
                   
                 CAATAA 
               
               
                   
               
               
                 OGT 
                 129 
                 AAGATTAATGTTCTT 
                 130 
                 CAGGTAAGTATAAGT 
                 131 
                 CCGCACGGCTCTGAA 
                 132 
                 TACGCGTGCCATCCA 
               
               
                   
                   
                 CATAAA 
                   
                 ATTCAA 
                   
                 ACTTAA 
                   
                 AATTAA 
               
               
                   
               
               
                 PAICS 
                 133 
                 CCCAAGGACTTCTAA 
                 134 
                 CTCGACTAACAGGGA 
                 135 
                 GCCCAAGGACTTCTA 
                 136 
                 CACGTGGAAATCTCC 
               
               
                   
                   
                 CAATAA 
                   
                 CTATAA 
                   
                 ACAATA 
                   
                 GTTATT 
               
               
                   
               
               
                 PPP2R5C 
                 137 
                 AACGAGCTGCTTTAA 
                 138 
                 CCCATTGGAACAAGT 
                 139 
                 CTGCTACTTCAGTAA 
                 140 
                 CTGGAAATATTGGGA 
               
               
                   
                   
                 GTGAAA 
                   
                 AAGAAA 
                   
                 GAATAA 
                   
                 AGTATA 
               
               
                   
               
               
                 PRDX4 
                 141 
                 AACCTGGTAGTGAAA 
                 142 
                 AAGCAAAGCGAAGAT 
                 143 
                 AAGGAGGACTTGGGC 
                 144 
                 ACAGCTGTGATCGAT 
               
               
                   
                   
                 CAATAA 
                   
                 TTCCAA 
                   
                 CAATAA 
                   
                 GGAGAA 
               
               
                   
               
               
                 PTTG1 
                 145 
                 AAGACCTGCAATAAT 
                 146 
                 CAGAATGGCTACTCT 
                 147 
                 TAAAGCATTCTTCAA 
                 148 
                 TCAGATGAATGCGGC 
               
               
                   
                   
                 CCAGAA 
                   
                 GATCTA 
                   
                 CAGAAA 
                   
                 TGTTAA 
               
               
                   
               
               
                 RAD51L1 
                 149 
                 CAGAGAGAAGACAGA 
                 150 
                 CCCGGCATGGGTAGC 
                 151 
                 CACAAGTAGGATCAA 
                 152 
                 CCCAGTTATCTTGAC 
               
               
                   
                   
                 TTCTTA 
                   
                 AAGAAA 
                   
                 GAACAA 
                   
                 GAATCA 
               
               
                   
               
               
                 RARA 
                 153 
                 TGGATAAAGAATAAA 
                 154 
                 CCACATCTTCATCAC 
                 155 
                 CTCCACCAAGTGCAT 
                 156 
                 CAGCTTCCAGTTAGT 
               
               
                   
                   
                 GTTCTA 
                   
                 CAGCAA 
                   
                 CATTAA 
                   
                 GGATAT 
               
               
                   
               
               
                 RBM4 
                 157 
                 ACCGAGCAATATAAT 
                 158 
                 CTCAGGAACCGTGGA 
                 159 
                 TACGCCTTACACCAT 
                 160 
                 CAGACTTGACCGAGC 
               
               
                   
                   
                 GAGCAA 
                   
                 CCTTAA 
                   
                 GAGCTA 
                   
                 AATATA 
               
               
                   
               
               
                 RECQL 
                 161 
                 CAGCTTGAAACTATT 
                 162 
                 TTGGAGATATATTCA 
                 163 
                 CATGCTGAAATGGTA 
                 164 
                 AAGAAAGAACATAAC 
               
               
                   
                   
                 AACGTA 
                   
                 GAATAA 
                   
                 AATAAA 
                   
                 AGAGTA 
               
               
                   
               
               
                 RRM1 
                 165 
                 CTGGTGGGTCTCTAG 
                 166 
                 AACGGATATATTGAG 
                 167 
                 CTGAGAGTATATAAC 
                 168 
                 CCGAGATTTCTCTTA 
               
               
                   
                   
                 AAGCAA 
                   
                 AATCAA 
                   
                 AACACA 
                   
                 CAATTA 
               
               
                   
               
               
                 SHFM1 
                 169 
                 CCGGTAGACTTAGGT 
                 170 
                 AAGAAGTGTTGAAGT 
                 171 
                 AACCCAGGATGGGAC 
                 172 
                 CTGCTTGGATTTATT 
               
               
                   
                   
                 CTGTTA 
                   
                 AACCTA 
                   
                 ACTAAA 
                   
                 TGTGTT 
               
               
                   
               
               
                 SPO11 
                 173 
                 CAGAGTGTACTTACC 
                 174 
                 TACATATATTATCTA 
                 175 
                 ACAACTAATGTTAAC 
                 176 
                 TACCTTCTACGATAC 
               
               
                   
                   
                 TAACAA 
                   
                 CATCAA 
                   
                 GCATAA 
                   
                 AACTAA 
               
               
                   
               
               
                 TMEM30A 
                 177 
                 AACGATTTAAAGGTA 
                 178 
                 CTCGAGATGATAGTC 
                 179 
                 ACCGGATAACACGGC 
                 180 
                 ATCGATGGCGATGAA 
               
               
                   
                   
                 CAACAA 
                   
                 AACTAA 
                   
                 CTTCAA 
                   
                 CTATAA 
               
               
                   
               
               
                 UBE2A 
                 181 
                 AACACCCTCTATGAA 
                 182 
                 AAGCGTGTTTCTGCA 
                 183 
                 CCCTAAGTGAATAAA 
                 184 
                 ATGGAACATTTAAAC 
               
               
                   
                   
                 ATCAAA 
                   
                 ATAGTA 
                   
                 CTCAAT 
                   
                 TTACAA 
               
               
                   
               
               
                 UBE2S 
                 185 
                 CCCGATGGCATCAAG 
                 186 
                 TCCCTCCAACTCTGT 
                 187 
                 CCGGCCGGCCGCAGC 
                 188 
                 CCGCCTGCTCTTGGA 
               
               
                   
                   
                 GTCTTT 
                   
                 CTCTAA 
                   
                 CATGAA 
                   
                 GAACTA 
               
               
                   
               
               
                 XAB2 
                 189 
                 CACGTACAACACGCA 
                 190 
                 CCGCGTGTACAAGTC 
                 191 
                 CAGCTACGTTTGTAC 
                 192 
                 CCGGACCTTGTCTTC 
               
               
                   
                   
                 GGTCAA 
                   
                 ACTGAA 
                   
                 ATCAAA 
                   
                 GAGGAA 
               
               
                   
               
               
                 XRCC2 
                 193 
                 CAGGGTACTACGCAA 
                 194 
                 TTGCAACGACACAAA 
                 195 
                 AGGGTACTACGCAAG 
                 196 
                 CACGATGTATACTTC 
               
               
                   
                   
                 GCCTTA 
                   
                 CTATAA 
                   
                 CCTTAA 
                   
                 CCAAAT 
               
               
                   
               
               
                 ABL1 
                 197 
                 AACACTCTAAGCATA 
                 198 
                 ACGCACGGACATCAC 
                 199 
                 CCAGTGGAGATAACA 
                 200 
                 CTGGGCGAATGTCTT 
               
               
                   
                   
                 ACTAAA 
                   
                 CATGAA 
                   
                 CTCTAA 
                   
                 ATTTAA 
               
               
                   
               
               
                 APAF1 
                 201 
                 AAGGGCAATGGAGAT 
                 202 
                 CAGTGAAGGTATGGA 
                 203 
                 CCGCATTCTGATGCT 
                 204 
                 TAGGCAGAGTATAAA 
               
               
                   
                   
                 AAATTA 
                   
                 ATATTA 
                   
                 TCGCAA 
                   
                 GTATTA 
               
               
                   
               
               
                 BAX 
                 205 
                 ATCATCAGATGTGGT 
                 206 
                 CAGCTCTGAGCAGAT 
                 207 
                 CAGGGTTTCATCCAG 
                 208 
                 CCGAGTGGCAGCTGA 
               
               
                   
                   
                 CTATAA 
                   
                 CATGAA 
                   
                 GATCGA 
                   
                 CATGTT 
               
               
                   
               
               
                 CARD4 
                 209 
                 CAGCCTGACAAGGTC 
                 210 
                 GCCCGCTCATTTGTT 
                 211 
                 AAGGCTGAGTACCAT 
                 212 
                 CACCCTGAGTCTTGC 
               
               
                   
                   
                 CGCAAA 
                   
                 AATAAA 
                   
                 GGGCTA 
                   
                 GTCCAA 
               
               
                   
               
               
                 CASP5 
                 213 
                 AAGAATCGCGTGGCT 
                 214 
                 TTCGTGATAAACCAC 
                 215 
                 TCAGCAGAATCTACA 
                 216 
                 ACGTGGCTGGACAAA 
               
               
                   
                   
                 CATCAA 
                   
                 ATGCTA 
                   
                 AATATA 
                   
                 CATCTA 
               
               
                   
               
               
                 CCT5 
                 217 
                 CACTGTAGATGCTAT 
                 218 
                 TAGCGTCCTTGTTGA 
                 219 
                 CCACTTCTGTGATTA 
                 220 
                 CCGCGATAATCGTGT 
               
               
                   
                   
                 AATAAA 
                   
                 CATAAA 
                   
                 AGTAAA 
                   
                 GGTGTA 
               
               
                   
               
               
                 CDKN1A 
                 221 
                 ATGATTCTTAGTGAC 
                 222 
                 CAGTTTGTGTGTCTT 
                 223 
                 CTGGCATTAGAATTA 
                 224 
                 CTCTGGCATTAGAAT 
               
               
                   
                   
                 TTTAAA 
                   
                 AATTAT 
                   
                 TTTAAA 
                   
                 TATTTA 
               
               
                   
               
               
                 CDKN3 
                 225 
                 CACAATCAAGATCTG 
                 226 
                 TCGGGACAAATTAGC 
                 227 
                 CACCAGTGTTATCAA 
                 228 
                 CTAGCATAATTTGTA 
               
               
                   
                   
                 TATCAA 
                   
                 TGCACA 
                   
                 CTTGAA 
                   
                 TTGAAA 
               
               
                   
               
               
                 CIDEA 
                 229 
                 CGGGTGCTGGATGAC 
                 230 
                 GAGAGTCACCTTCGA 
                 231 
                 ACGCATTTCATGATC 
                 232 
                 CACGCATTTCATGAT 
               
               
                   
                   
                 AAGGAA 
                   
                 CTTGTA 
                   
                 TTGGAA 
                   
                 CTTGGA 
               
               
                   
               
               
                 CRIP2 
                 233 
                 GAGCCTTGTGCTGTC 
                 234 
                 CTGGCACAAGTTCTG 
                 235 
                 CCCACCTGCCAGTGT 
                 236 
                 ACGGTTTGAGGATTG 
               
               
                   
                   
                 AATAAA 
                   
                 CCTCAA 
                   
                 TATTTA 
                   
                 CAGAAA 
               
               
                   
               
               
                 CUL1 
                 237 
                 AACGTAGTTATCAGC 
                 238 
                 ACCGACAGCACTCAA 
                 239 
                 CTCAGGATTGATACA 
                 240 
                 CGGGTTCGAGTACAC 
               
               
                   
                   
                 GATTCA 
                   
                 ATTAAA 
                   
                 TTTCAA 
                   
                 CTCTAA 
               
               
                   
               
               
                 CYP1A2 
                 241 
                 CAGCCTAACTTACAT 
                 242 
                 CCAGCCTAACTTACA 
                 243 
                 CGCCGATGGCACTGC 
                 244 
                 CCCACAGGAGAAGAT 
               
               
                   
                   
                 TCTTAA 
                   
                 TTCTTA 
                   
                 CATTAA 
                   
                 TGTCAA 
               
               
                   
               
               
                 DNMT1 
                 245 
                 CCCATCGGMCCGCG 
                 246 
                 TCGCTTATCAACTAA 
                 247 
                 TCCCGAGTATGCGCC 
                 248 
                 CCCAATGAGACTGAC 
               
               
                   
                   
                 CGAAA 
                   
                 TGATTT 
                   
                 CATATT 
                   
                 ATCAAA 
               
               
                   
               
               
                 ERCC4 
                 249 
                 CAGCACCTCGATGTTT 
                 250 
                 CTCGCCGTGTAACAA 
                 251 
                 AGCAATGACATTAGT 
                 252 
                 CGCAAGAGTATCAGT 
               
               
                   
                   
                 ATAAA 
                   
                 ATGAAA 
                   
                 TCCAAA 
                   
                 GATTTA 
               
               
                   
               
               
                 FANCE 
                 253 
                 AACGCCGAGGAGAGCT 
                 254 
                 TAGCCTGAGGATAAA 
                 255 
                 CTGACTTGAATAATT 
                 256 
                 TCGAATCTGGATGAT 
               
               
                   
                   
                 TGTAA 
                   
                 GGCTGA 
                   
                 TATCAA 
                   
                 GCTAAA 
               
               
                   
               
               
                 GSTT1 
                 257 
                 AAGCAGGAATGGCTTG 
                 258 
                 CTGATTAAAGGTCAG 
                 259 
                 CTGAGGCCTTGTGTC 
                 260 
                 CCCGTGGGTGCTGGC 
               
               
                   
                   
                 CTTAA 
                   
                 CACTTA 
                   
                 CTTTAA 
                   
                 TGCCAA 
               
               
                   
               
               
                 GSTZ1 
                 261 
                 CGCGCTGAAATTTGGC 
                 262 
                 ACGGTGCCCATCAAT 
                 263 
                 CTGAAATTTGGCGTG 
                 264 
                 TACCATCAGCTCCAT 
               
               
                   
                   
                 GTGAA 
                   
                 CTCATA 
                   
                 AATTAA 
                   
                 CAACAA 
               
               
                   
               
               
                 GTF2H5 
                 265 
                 ATGGACCATTTAGGAA 
                 266 
                 CAGGAGCGAGTGGGT 
                 267 
                 CACGTCTTTGTAATA 
                 268 
                 TTCCCTTACCCAGAA 
               
               
                   
                   
                 TTATA 
                   
                 GAATTA 
                   
                 GCAGAA 
                   
                 ATGAAA 
               
               
                   
               
               
                 KPNA2 
                 269 
                 ACGAATTGGCATGGTG 
                 270 
                 CCGGGCTGGTTTGAT 
                 271 
                 ACCAGTGGTGGAACA 
                 272 
                 CAGATTCAAGAACAA 
               
               
                   
                   
                 GTGAA 
                   
                 TCCGAA 
                   
                 GTTGAA 
                   
                 GGGAAA 
               
               
                   
               
               
                 MRPS12 
                 273 
                 CAGGACCACTATTAAG 
                 274 
                 TTCCATCAGGACCAC 
                 275 
                 CTGCTGGGACAAGAC 
                 276 
                 CACGTTTACCCGCAA 
               
               
                   
                   
                 CCATA 
                   
                 TATTAA 
                   
                 ACTGTA 
                   
                 GCCGAA 
               
               
                   
               
               
                 MSH5 
                 277 
                 AAGAAAGATATTGTTT 
                 278 
                 CACCTTCATGATCGA 
                 279 
                 TAG GAAGACTCCCGG 
                 280 
                 TTGCCAGACATTAGT 
               
               
                   
                   
                 CTTTA 
                   
                 CCTCAA 
                   
                 ATTCTA 
                   
                 GGATAA 
               
               
                   
               
               
                 NFKB1 
                 281 
                 CTGGGTATACTTCATG 
                 282 
                 GACGCCATCTATGAC 
                 283 
                 ACCGTGTAAACCAAA 
                 284 
                 CGCGGTGACAGGAGA 
               
               
                   
                   
                 TGACA 
                   
                 AGTAAA 
                   
                 GCCCTA 
                   
                 CGTGAA 
               
               
                   
               
               
                 PTEN 
                 285 
                 AAGATTTATGATGCAC 
                 286 
                 CAATTTGAGATTCTA 
                 287 
                 ACGGGAAGACAAGTT 
                 288 
                 TCGGCTTCTCCTGAA 
               
               
                   
                   
                 TTATT 
                   
                 CAGTAA 
                   
                 CATGTA 
                   
                 AGGGAA 
               
               
                   
               
               
                 SMARCA4 
                 289 
                 CCCGTGGACTTCAAGA 
                 290 
                 CCGCGCTACAACCAG 
                 291 
                 TCACTGGATGTCAAA 
                 292 
                 CCGCAGTTTGGAGTC 
               
               
                   
                   
                 AGATA 
                   
                 ATGAAA 
                   
                 CAGTAA 
                   
                 ACTGTA 
               
               
                   
               
               
                 SND1 
                 293 
                 ATCCACCGTGTTGCAG 
                 294 
                 CAGGCTGAACCTGTG 
                 295 
                 ACGGTGGACTACATT 
                 296 
                 TCGAAAGAAGCTGAT 
               
               
                   
                   
                 ATATA 
                   
                 GCGCTA 
                   
                 AGACCA 
                   
                 TGGGAA 
               
               
                   
               
               
                 SOX4 
                 297 
                 AAGGACAGACGAAGAG 
                 298 
                 CACGGTCAAACTGAA 
                 299 
                 TCCTTTCTACTTGTC 
                 300 
                 CCGCGAGAAACTTGC 
               
               
                   
                   
                 TTTAA 
                   
                 ATGGAT 
                   
                 GCTAAA 
                   
                 ATTGGA 
               
               
                   
               
               
                 SUMO1 
                 301 
                 CAGTTACCTAATCATG 
                 302 
                 CTGAATCAAGGATTT 
                 303 
                 CTGAAGTGCCTTCTG 
                 304 
                 CAGGTTGAAGTCAAG 
               
               
                   
                   
                 TTGAA 
                   
                 AATTAA 
                   
                 AATCAA 
                   
                 ATGACA 
               
               
                   
               
               
                 TARS 
                 305 
                 CACCGTTATTGCTAAA 
                 306 
                 GAGGAACAGCGTTTC 
                 307 
                 ACACCGTTATTGCTA 
                 308 
                 AAGCCGATTGGTGCT 
               
               
                   
                   
                 GTAAA 
                   
                 CGTAAA 
                   
                 AAGTAA 
                   
                 GGTGAA 
               
               
                   
               
               
                 TNFRSF10A 
                 309 
                 ATCAAACTTCATGATC 
                 310 
                 CCGGGTCCACAAGAC 
                 311 
                 CAGGCAATGGACATA 
                 312 
                 CAGGAACTTTCCGGA 
               
               
                   
                   
                 AATCA 
                   
                 CTTCAA 
                   
                 ATATAT 
                   
                 ATGACA 
               
               
                   
               
               
                 TNFSF8 
                 313 
                 AAGGACTCTCTCACAC 
                 314 
                 ACCCATATCAAGGGT 
                 315 
                 TAGGGTGTGGTCACT 
                 316 
                 CACTAGGAGGCTGAT 
               
               
                   
                   
                 AGGAA 
                   
                 GACTAA 
                   
                 CTCAAT 
                   
                 CTTGTA 
               
               
                   
               
               
                 TP53 
                 317 
                 CAGCATCTTATCCGAG 
                 318 
                 TTGCAGTTAAGGGTT 
                 319 
                 TTGGTCGACCTTAGT 
                 320 
                 CAGAGTGCATTGTGA 
               
               
                   
                   
                 TGGAA 
                   
                 AGTTTA 
                   
                 ACCTAA 
                   
                 GGGTTA 
               
               
                   
               
               
                 XPC 
                 321 
                 CCGGCTGGTATTGTCT 
                 322 
                 TAGCAAATGGCTTCT 
                 323 
                 TCGGAGGGCGATGAA 
                 324 
                 CCAGTGGAGATAGAG 
               
               
                   
                   
                 CTACA 
                   
                 ATCGAA 
                   
                 ACGTTT 
                   
                 ATTGAA 
               
               
                   
               
               
                 XRCC3 
                 325 
                 CAGAATTATTGCTGCA 
                 326 
                 GAGACACTTAAGGGA 
                 327 
                 CCGCTGTGAATTTGA 
                 328 
                 AAGCCAAACTGAAAT 
               
               
                   
                   
                 ATTAA 
                   
                 AATTAA 
                   
                 CAGCCA 
                   
                 CGGTAA 
               
               
                   
               
               
                     indicates data missing or illegible when filed 
               
            
           
         
       
     
     
       
         
           
               
               
               
             
               
                 TABLE 3 
               
               
                   
               
               
                 Symbol 
                 Entrez ID 
                 Full Name 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
            
               
                 Genes conferring sensitivity to oxaliplatin 
               
            
           
           
               
               
               
            
               
                 BCL10 
                 8915 
                 B-cell CLL/lymphoma 10 
               
               
                 BCL2L10 
                 10017 
                 BCL2-like 10 (apoptosis facilitator) 
               
               
                 BFAR 
                 51283 
                 bifunctional apoptosis regulator 
               
               
                 BRIP1 
                 83990 
                 BRCA1 interacting protein C-terminal 
               
               
                   
                   
                 helicase 1 
               
               
                 CHAF1A 
                 10036 
                 chromatin assembly factor 1, subunit A 
               
               
                   
                   
                 (p150) 
               
               
                 CUL4B 
                 8450 
                 cullin 4B 
               
               
                 DFFA 
                 1676 
                 DNA fragmentation factor, 45kDa, alpha 
               
               
                   
                   
                 polypeptide 
               
               
                 IL8 
                 357.6 
                 interleukin 8 
               
               
                 LTBR 
                 4055 
                 Lymphotoxin beta receptor (TNFR super- 
               
               
                   
                   
                 family, member 3) 
               
               
                 MBD2 
                 8932 
                 methyl-CpG binding domain protein 2 
               
               
                 MBD4 
                 8930 
                 methyl-CpG binding domain protein 4 
               
               
                 MCM3 
                 4172 
                 minichromosome maintenance complex 
               
               
                   
                   
                 component 3 
               
               
                 MCM4 
                 4173 
                 minichromosome maintenance complex 
               
               
                   
                   
                 component 4 
               
               
                 MCM6 
                 4175 
                 minichromosome maintenance complex 
               
               
                   
                   
                 component 6 
               
               
                 MPG 
                 4350 
                 N-methylpurine-DNA glycosylase 
               
               
                 MSH4 
                 4438 
                 mutS homolog 4 ( E. coli ) 
               
               
                 NHEJ1 
                 79840 
                 nonhomologous end-joining factor 1 
               
               
                 PRDX4 
                 10549 
                 peroxiredoxin 4 
               
               
                 PTTG1 
                 9232 
                 pituitary tumor-transforming 1 
               
               
                 RAD51L1 
                 5890 
                 RAD51-like 1 ( S. cerevisiae ) 
               
               
                 RRM1 
                 6240 
                 ribonucleotide reductase M1 
               
               
                 SHFM1 
                 7979 
                 split hand/foot malformation (ectrodactyly) 
               
               
                   
                   
                 type 1 
               
               
                 TMEM30A 
                 55754 
                 transmembrane protein 30A 
               
            
           
           
               
            
               
                 Genes conferring resistance to oxaliplatin 
               
            
           
           
               
               
               
            
               
                 CDKN1A 
                 1026 
                 Cyclin-dependent kinase inhibitor 1A 
               
               
                   
                   
                 (p21, Cip1) 
               
               
                 KPNA2 
                 3838 
                 karyopherin alpha 2 (RAG cohort 1, importin 
               
               
                   
                   
                 alpha 1) 
               
               
                 SUMO1 
                 7341 
                 SMT3 suppressor of mif two 3 homolog 1 
               
               
                   
                   
                 ( S. cerevisiae ) 
               
               
                 TP53 
                 7157 
                 Tumor protein p53 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
               
             
               
                 TABLE 4 
               
               
                   
               
               
                   
                   
                   
                 Median Fold 
                   
                 Median Fold 
               
               
                   
                   
                   
                 Change IC50 
                   
                 Change IC50 
               
               
                   
                   
                   
                 Oxaliplatin 
                   
                 Oxaliplatin 
               
               
                   
                   
                   
                 (Log 2 ) from 
                   
                 (Log 2 ) from 
               
               
                 Symbol 
                 Entrez ID 
                 Description 
                 HTS 
                 RSA P-value 
                 Validation 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
               
            
               
                 LTBR 
                 4055 
                 Lymphotoxin beta receptor (TNFR superfamily, member 3) 
                 1.56 
                 7.85E−04 
                 0.83 
               
               
                 TMEM30A 
                 55754 
                 transmembrane protein 30A 
                 1.49 
                 9.85E−05 
                 0.98 
               
               
                 MCM3 
                 4172 
                 minichromosome maintenance complex component 3 
                 1.17 
                 1.31E−03 
                 1.53 
               
               
                 SHFM1 
                 7979 
                 split hand/foot malformation (ectrodactyly) type 1 
                 1.11 
                 3.01E−04 
                 0.69 
               
               
                 MBD4 
                 8930 
                 methyl-CpG binding domain protein 4 
                 1.10 
                 1.50E−04 
                 1.37 
               
               
                 NHEJ1 
                 79840 
                 nonhomologous end-joining factor 1 
                 1.09 
                 6.72E−04 
                 1.45 
               
               
                 BFAR 
                 51283 
                 bifunctional apoptosis regulator 
                 0.86 
                 1.03E−03 
                 0.33 
               
               
                 PTTG1 
                 9232 
                 pituitary tumor-transforming 1 
                 0.83 
                 1.59E−03 
                 2.93 
               
               
                 CUL4B 
                 8450 
                 cullin 4B 
                 0.74 
                 2.75E−03 
                 1.68 
               
               
                 BRIP1 
                 83990 
                 BRCA1 interacting protein C-terminal helicase 1 
                 0.72 
                 4.09E−04 
                 1.63 
               
               
                 PRDX4 
                 10549 
                 peroxiredoxin 4 
                 0.64 
                 1.65E−03 
                 1.25 
               
               
                 CDKN1A 
                 1026 
                 Cyclin-dependent kinase inhibitor 1A (p21, Cip1) 
                 −1.51 
                 1.02E−13 
                 −0.62 
               
               
                 TP53 
                 7157 
                 Tumor protein p53 
                 −1.51 
                 2.27E−05 
                  0.95 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
               
               
               
               
             
               
                 TABLE 4 
               
               
                   
               
               
                   
                 SEQ 
                   
                 SEQ 
                   
                 SEQ 
                   
                 SEQ 
                   
               
               
                   
                 ID 
                 siRNA Sequence 1 
                 ID 
                 siRNA Sequence 2 
                 ID 
                 siRNA Sequence 3 
                 ID 
                 siRNA Sequence 4 
               
               
                 Symbol 
                 NO. 
                 from Validation 
                 NO. 
                 from Validation 
                 NO. 
                 from Validation 
                 NO. 
                 from Validation 
               
               
                   
               
             
            
               
                 LTBR 
                 329 
                 GAACCAAUUUAUCACCCAU 
                 330 
                 CCACAUGUGCCGAGAAUUC 
                 331 
                 GCACUGAAGCCGAGCUCAA 
                 332 
                 AUACUUCCCUGACUUGGUA 
               
               
                   
               
               
                 TMEM30A 
                 333 
                 GCGAUGAACUAUAACGCGA 
                 334 
                 CCAUCGUCGUUACGUGAAA 
                 335 
                 GCACAGAGGAUGUCGCUAA 
                 336 
                 GCGAGAUCGAGAUUGAUUA 
               
               
                   
               
               
                 MCM3 
                 337 
                 CUGAUUGCCUGUAAUGUUA 
                 338 
                 GCAGGUAUGACCAGUAUAA 
                 339 
                 GACCAUAGAGCGACGUUAU 
                 340 
                 CUAACCGGCUUCUGAACAA 
               
               
                   
               
               
                 SHFM1 
                 341 
                 GUUAUAAGAUGGAGACUUC 
                 342 
                 AGACUGGGCUGGCUUAGAU 
                 343 
                 GUUACGAGCUGAACUAGAG 
                 344 
                 CAAUGUAGAGGAUGACUUC 
               
               
                   
               
               
                 MBD4 
                 345 
                 GAAGAUUUGAUGUGUACUU 
                 346 
                 GGAACAGAAUGCCGUAAGU 
                 347 
                 GAAGAUACCAUCCCACGAA 
                 348 
                 UAACUUUACUUCCACUCAU 
               
               
                   
               
               
                 NHEJ1 
                 349 
                 GGGCUACGCUGAUUCGAGA 
                 350 
                 GAGGGAGCUAGCAACGUUA 
                 351 
                 CCUUCAGAUUCUUCGUAAA 
                 352 
                 AGAAAGAGUCCACGGGUAC 
               
               
                   
               
               
                 BFAR 
                 353 
                 UAACACAGGCCGAGCGAAU 
                 354 
                 GCUACGACAUCCUGGUUAA 
                 355 
                 AGAAAUAUGGGAAUGAUCA 
                 356 
                 GGACAUCACGGUUUCUCAU 
               
               
                   
               
               
                 PTTG1 
                 357 
                 GCUGUGACAUAGAUAUUUA 
                 358 
                 UGGGAGAUCUCAAGUUUCA 
                 359 
                 GGGAAUCCAAUCUGUUGCA 
                 360 
                 GUUGAAUUGCCACCUGUUU 
               
               
                   
               
               
                 CUL4B 
                 361 
                 UAAAUAACCUCCUUGAUGA 
                 362 
                 CAGAAGUCAUUAAUUGCUA 
                 363 
                 CGGAAAGAGUGCAUCUGUA 
                 364 
                 GCUAUUGGCCGACAUAUGU 
               
               
                   
               
               
                 BRIP1 
                 365 
                 AGUCAAGAGUCAUCGAAUA 
                 366 
                 GAUAGUAUGGUCAACAAUA 
                 367 
                 UAACCCAAGUCGCUAUAUA 
                 368 
                 GUGCAAAGCCUGGGAUAUA 
               
               
                   
               
               
                 PRDX4 
                 369 
                 GGACUAUGGUGUAUACCUA 
                 370 
                 CGUGGGAAAUACUUGGUUU 
                 371 
                 GGAUUCCACUUCUUUCAGA 
                 372 
                 GAUGAGACACUACGUUUGG 
               
               
                   
               
               
                 CDKN1A 
                 373 
                 CGACUGUGAUGCGCUAAUG 
                 374 
                 CCUAAUCCGCCCACAGGAA 
                 375 
                 CGUCAGAACCCAUGCGGCA 
                 376 
                 AGACCAGCAUGACAGAUUU 
               
               
                   
               
               
                 TP53 
                 377 
                 GAAAUUUGCGUGUGGAGUA 
                 378 
                 GUGCAGCUGUGGGUUGAUU 
                 379 
                 GCAGUCAGAUCCUAGCGUC 
                 380 
                 GGAGAAUAUUUCACCCUUC