Abstract:
The present invention features transgenic non-human mammalian animals being genetically modified to develop cancer. The invention also relates to methods for identifying genes or genetic elements that are potentially related to human cancers using an chromosomally unstable animal model. Information on such genetic alterations can be used to predict cancer therapeutic outcomes and to stratify patient populations to maximize therapeutic efficacy.

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
       [0001]    This application claims the benefit of and priority to U.S. Provisional Application No. 60/931,294, filed on May 21, 2007, the contents of which is hereby incorporated by reference in its entirety. 
     
    
     GOVERNMENT SUPPORT 
       [0002]    The work described herein was funded, in whole or in part, by Grant Number CA84628 (RO1) and CA84313 (UO1). The United States government may have certain rights in the invention. 
     
    
     FIELD OF THE INVENTION 
       [0003]    The present invention relates generally to the use of a genome unstable animal cancer model for cancer gene discovery. 
       BACKGROUND INFORMATION 
       [0004]    Cancer is a genetic disease driven by the stochastic acquisition of mutations and shaped by natural selection. Genomic instability, a hallmark of many human cancers, propagates these mutations, allowing cells to overcome critical barriers to unregulated growth, and may therefore herald a defining event in malignant transformation. Genomic instability is manifested by chromosomal aberrations, such as translocations and amplifications. How and when during the course of tumor progression significant genomic instability arises, and whether a cancer can be cured or even contained after that point, represent pivotal and largely unanswered questions. 
         [0005]    Animal models for human carcinomas are valuable tools for the investigation and development of cancer therapies. Murine models having oncogenes incorporated into its genome, or tumor suppressor genes suppressed have been widely used for human cancer research. However, an impediment towards maximal utilization of murine models for guiding human cancer gene discovery efforts is the relatively benign cytogenetic profiles of most standard genetically engineered mouse models of cancer (see, e.g., N. Bardeesy, et al.,  Proc Natl Acad Sci USA  103 (15), 5947 (2006); M. Kim, et al.,  Cell  125 (7), 1269 (2006); L. Zender, et al.,  Cell  125 (7), 1253 (2006); A. Sweet-Cordero, et al.,  Genes Chromosomes Cancer  45 (4), 338 (2006)). These models do not reflect the global chromosomal aberrations associated with many types of human cancers. 
         [0006]    Several cancer-prone murine models have recently been developed that more closely simulate the rampant chromosomal instability of human cancers. For example, Artandi et al. describe the development of epithelial cancers in a telomerase-definition p53-mutant mouse model ( Nature  406 (6796), 641 (2000)); Zhu et. al describe oncogene translocation and amplification in a mouse model that is deficient in both p53 and nonhomologous end-joining (NHEJ) ( Cell  109 (7), 811 (2002)); Olive et. al describe a Li-Fraumeni Syndrome mouse model having dominant p53 mutant alleles ( Cell  119 (6), 847 (2004)); Lang et. al describe a Li-Fraumeni Syndrome mouse model having p53 missense mutations ( Cell  119 (6), 861 (2004)); and Hingorani et. al describe a mouse model of pancreatic ductal adenocarcinoma, expressing mutant forms of TP53 and KRAS2 ( Cancer Cell  7 (5), 469 (2005)). However, the frequency of chromosomal aberrations in these mouse models are relatively low, and the transgenic mice do not necessarily develop malignant cancer. To facilitate oncogenomic anlayses, there is a need to create new mammal models that are genetically modified to develop cancer, having chromosomal aberrations at a frequency that is comparable to human cancers. 
       SUMMARY OF THE INVENTION 
       [0007]    Highly rearranged and mutated cancer genomes present major challenges in the identification of pathogenetic events driving the cancer process. Here, we engineered lymphoma-prone mice with chromosomal instability to assess the utility of animal models in cancer gene discovery and the extent of cross-species overlap in cancer-associated copy number alterations. Integrating with targeted re-sequencing, our comparative oncogenomic studies identified FBXW7 and PTEN as commonly deleted or mutated tumor suppressors in human T-cell acute lymphoblastic leukemia/lymphoma (T-ALL). More generally, the murine cancers acquire widespread recurrent clonal amplifications and deletions targeting loci syntenic to alterations present in not only human T-ALL but also diverse tumors of hematopoietic, mesenchymal and epithelial types. These results thus support the view that murine and human tumors experience common biological processes driven by orthologous genetic events as they evolve towards a malignant phenotype. The highly concordant nature of genomic events encourages the use of genome unstable animal cancer models in the discovery of biologically relevant driver events in human cancer. 
         [0008]    In one aspect, the invention provides a non-human transgenic mammal that is genetically modified to develop cancer, such that the genome of a cancer cell from the mammal comprises chromosomal structural aberrations at a frequency that is at least 5-fold higher than the frequency of chromosomal structural aberrations in such mammal without the genetic modification. In certain embodiments, the mammal is a rodent. In certain embodiments, the mammal is a mouse. 
         [0009]    In certain embodiments, the mammal comprises engineered inactivation of: at least one allele of one or more genes encoding a protein involved in DNA repair function (such as a protein involved in non-homologous end joining (NHEJ), a protein involved in homologous recombination, or a DNA repair helicase), and at least one allele of one or more genes encoding a component that synthesizes and maintains telomere length. Alternatively, the mammal may comprise engineered inactivation of: at least one allele of one or more genes encoding a protein involved in DNA repair function and at least one allele of one or more genes encoding a DNA damage checkpoint protein. Alternatively, the mammal may comprise engineered inactivation of: at least one allele of one or more genes encoding a DNA damage checkpoint protein and at least one allele of one or more genes encoding a component that synthesizes and maintains telomere length. 
         [0010]    In certain embodiments, the genome of the mammal further comprises at least one additional cancer-promoting modification, such as an activated oncogene, an inactivated tumor suppressor gene, or both. 
         [0011]    In another aspect, the invention provides a method of identifying a chromosomal region of interest for the identification of a gene or genetic element that is potentially related to human cancer, comprising the step of: identifying a DNA copy number alteration in a population of cancer cells from a non-human mammal that is engineered to produce chromosomal instability. The chromosomal region of the DNA copy number alteration is a chromosomal region of interest for identifying a gene or genetic element that is potentially related to human cancer. 
         [0012]    In certain embodiments, the DNA copy number alteration is recurrent in two or more cancer cells from the non-human mammal. The DNA copy number alteration can be a DNA gain or a DNA loss. 
         [0013]    In another aspect, the invention provides a method of identifying a chromosomal region of interest for the identification of a gene or genetic element that is potentially related to human cancer, comprising the step of: identifying a chromosomal structural aberration in a population of cancer cells from a non-human mammal that is engineered to produce genome instability. A chromosomal region containing the chromosomal structural aberration is a chromosomal region of interest for identifying a gene or genetic element that is potentially related to human cancer. 
         [0014]    In certain embodiments, the method further comprises the steps of: (1) identifying a DNA copy number alteration in the population of cancer cells from the non-human mammal, and (2) identifying a chromosomal region in the genome of the cancer cell of the non-human mammal that contains a chromosomal structural aberration and a DNA copy number alteration. The chromosomal region containing a chromosomal structural aberration and a DNA copy number alteration is a chromosomal region of interest for identifying a gene and genetic element that is potentially related to human cancer. In certain embodiments, the method further comprises the step of determining the uniform copy number segment boundary of the DNA copy number alteration. 
         [0015]    In another aspect, the invention provides a method for identifying a potential human cancer-related gene, comprising the steps of: (a) identifying a chromosomal region of interest (e.g., comprising a gene or genetic element that is potentially related to human cancer); (b) identifying a gene or genetic element within the chromosomal region of interest in the non-human mammal, and (c) identifying a human gene or genetic element that corresponds to the gene or genetic element identified in step (b). The human gene or genetic element is a potential human cancer-related gene or genetic element. In certain embodiments, the human gene is orthologous, paralogous, or homologous to the gene or genetic element identified in step (b). In certain embodiments, the method further comprises the step of detecting a mutation in the non-human mammalian gene or genetic element identified in step (b), the human gene or genetic element identified in step (c), or both. 
         [0016]    In another aspect, the invention provides a method of identifying a potential human cancer-related gene or genetic element, comprising the steps of: (a) detecting a DNA copy number alteration in a population of cancer cells from a non-human mammal that is engineered to produce genome instability, (b) identifying a gene or genetic element located within the boundaries of the DNA copy number alteration detected in step (a), and (c) identifying a human gene or genetic element that corresponds to the gene or genetic element identified in step (b) and that is located within the boundaries of a DNA copy number alteration or of a chromosomal structural aberration in a human cancer cell. The human gene or genetic element identified in step (c) is a gene or genetic element potentially related to human cancer. 
         [0017]    In another aspect, the invention provides a method of identifying a potential human cancer-related gene or genetic element, comprising the steps of (a) detecting a chromosomal structural aberration in a population of cancer cells from a non-human mammal that is engineered to produce genome instability, (b) identifying a gene or genetic element located at the site of the chromosomal structural aberration detected in step (a), and (c) identifying a human gene or genetic element that corresponds to the gene or genetic element identified in step (b) and that is located within the boundaries of a DNA copy number alteration or at the site of a chromosomal structural aberration in a human cancer cell. The human gene or genetic element identified in step (c) is a gene or genetic element potentially related to human cancer. In certain embodiments, the method further comprises the step of detecting a mutation in the non-human mammalian gene or genetic element identified in step (b), the human gene or genetic element identified in step (c), or both. 
         [0018]    In certain embodiments, the method further comprises the step of defining the minimum common region (MCR) of a recurrent gene copy number alteration. In certain embodiments, the MCR is defined by boundaries of overlap between two or more samples. In certain embodiments, the MCR is defined by the boundaries of a single tumor against a background of larger alteration in at least one other tumor. 
         [0019]    In another aspect, the invention provides a method for identifying subjects with T-cell acute lymphoblastic leukemia (T-ALL) who may have a decreased response to γ-secretase inhibitor therapy, comprising detecting the expression or activity of FBXW7 in a tumor cell from the subject. A decreased expression or activity of FBXW7, as compared to a control, is indicative that the subject may have a decreased response to γ-secretase inhibitor therapy. 
         [0020]    In certain embodiments, the method further comprises detecting the expression or activity of NOTCH1 in a tumor cell from the subject. An increased expression or activity of NOTCH1, as compared to a control, is indicative that the subject may have a decreased response to γ-secretase inhibitor therapy. 
         [0021]    In another aspect, the invention provides a method for identifying subjects with T-ALL that may benefit from treatment with a PI3K pathway inhibitor, comprising detecting the expression or activity of PTEN in a tumor cell from the subject. A decreased expression or activity of PTEN, as compared to a control, is indicative that the subject may benefit from a treatment with a PI3K inhibitor. In certain embodiments, the method further comprises treating the subject with a PI3K inhibitor. 
         [0022]    In another aspect, the invention provides a method of assessing whether a subject is afflicted with cancer or at risk for developing cancer, comprising: determining the expression or activity level of at least one cancer gene or candidate cancer gene located in an amplified MCR in Table 1 in a biological sample from the subject. An increase in the expression or activity the gene, as compared to a control, indicates that the subject is afflicted with cancer or at risk for developing cancer. Alternatively, if there is a decrease in the expression or activity of a cancer gene or candidate cancer gene located in a deleted MCR in Table 1, as compared to a control, the decreased expression or activity level also indicates that the subject is afflicted with cancer or at risk for developing cancer. 
         [0023]    In another aspect, the invention provides a method of assessing whether a subject is afflicted with cancer or at risk for developing cancer, the method comprising: determining the copy number of at least one amplified minimal common region (MCR) listed in Table 1 in a biological sample from the subject. An increased copy number of the MCR in the sample, as compared to the normal copy number of the MCR, indicates that the subject is afflicted with cancer or at risk for developing cancer. Alternatively, a decreased copy number of a deleted MCR (also listed in Table 1) in the sample, as compared to the normal copy number of the MCR, also indicates that the subject is afflicted with cancer or at risk for developing cancer. The normal copy number of an MCR is typically one per chromosome. 
         [0024]    In another aspect, the invention provides a method for monitoring the progression of cancer in a subject, the method comprising: a) determining in a biological sample from the subject at a first point in time, the expression or activity level of a cancer gene or a candidate cancer gene listed in Table 1; b) repeating step a) at a subsequent point in time; and c) comparing the expression or activity of the gene in steps a) and b), and therefrom monitoring the progression of cancer in the subject. 
         [0025]    In another aspect, the invention provides a method of assessing the efficacy of a test agent for treating a cancer in a subject, comprising: a) determining the expression or activity level of at least one cancer gene or a candidate cancer gene located in an amplified MCR in Table 1 in a biological sample from the subject in the presence of the test agent; and b) determining the expression or activity level of the gene in a biological sample from the subject in the absence of the test agent. A decreased expression or activity of the gene in step (a), as compared to that of (b), is indicative of the test agent&#39;s potential efficacy for treating the cancer in the subject. Alternatively, if the test agent increases the expression or activity of at least one cancer gene or a candidate cancer gene located in a deleted MCR in Table 1, the test agent is also potentially effective for treating the cancer in a subject. 
         [0026]    In another aspect, the invention provides a method of assessing the efficacy of a therapy for treating cancer in a subject, the method comprising: a) determining the expression or activity level of at least one cancer gene or a candidate cancer gene located in an amplified MCR in Table 1 in a biological sample from the subject prior to providing at least a portion of the therapy to the subject; and b) determining the expression or activity level of the gene in a biological sample from the subject following provision of the portion of the therapy. A decreased expression or activity of the gene in step (a), as compared to that of (b), is indicative of the therapy&#39;s efficacy for treating the cancer in the subject. Alternatively, if the therapy increases the expression or activity of at least one cancer gene or a candidate cancer gene located in a deleted MCR in Table 1, the therapy is also potentially effective for treating the cancer in a subject. 
         [0027]    In another aspect, the invention provides a method of treating a subject afflicted with cancer comprising administering to the subject an agent that decreases the expression or activity level of at least one cancer gene or candidate cancer gene located in am amplified MCR in Table 1. Alternatively, the invention provides a method of treating a subject afflicted with cancer comprising administering to the subject an agent that increases the expression or activity level of at least one cancer gene or candidate cancer gene located in a deleted MCR in Table 1. 
         [0028]    In certain embodiments, the agent is an antibody, or its antigen-binding fragment thereof, that specifically binds to a cancer gene or candidate cancer gene listed in Table 1. 
         [0029]    In another aspect, the invention provides a method of assessing whether a subject is afflicted with cancer or at risk for developing cancer, the method comprising: determining the copy number of at least one minimal common region (MCR) listed in Table 5 in a biological sample from the subject. A change of copy number of the MCR in the sample, as compared to the normal copy number of the MCR, indicates that the subject is afflicted with cancer or at risk for developing cancer. The normal copy number of an MCR is typically one per chromosome. 
         [0030]    In certain embodiments, the cancer is lymphoma. In certain embodiments, the lymphoma is T-ALL. 
         [0031]    In another aspect, the invention provides a method of assessing whether a subject is afflicted with cancer or at risk for developing cancer, by comparing the copy number of an MCR, identified using a genome-unstable non-human mammal model (including a genome-unstable mouse model of the invention), with the normal copy number of the MCR. The normal copy number of an MCR is typically one per chromosome. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0032]      FIG. 1 : Spectral Karyotype (SKY) profiles of TKO tumors. G-band and SKY images of representative metaphases for selected TKO tumors with and without telomere dysfunction.  FIG. 1A  represents G0 (mTerc +/+ or +/−) and  FIG. 1B  represents G1-G4 (mTerc−/−) TKO tumors. The pictures show an overall increase in frequency of chromosome structural aberrations in TKO tumors with telomere dysfunction. Nonreciprocal translocations and chromosomal fragments are marked by arrows.  FIG. 1C  shows representative array-CGH Log 2 ratio plots of syntenic murine TKO (left; A689) and human (right; HPB-ALL) TCRB deletions. Y axis, log 2 ratio of copy number (normal set at log 2=0); amplifications are above and deletions are below this axis; X axis, chromosome position. 
           [0033]      FIG. 2 . Characterization of the TKO model.  FIG. 2A  is a graph showing Kaplan-Meier curve of thymic lymphoma-free survival for G3-G4 TKO mice on p53 wildtype, heterozygous and null background.  FIG. 2B  shows the loss of heterozygosity for p53 using PCR; N, normal; T, tumor.  FIG. 2C  is a representative FACS profile of TKO tumor, using antibodies against cell surface markers CD4 and CD8.  FIG. 2D  is a representative SKY images from metaphase spreads from G0 (top) and G1-G4 (bottom) thymic lymphomas. Of equal number of metaphase spreads (90), 410 aberrations per 4533 chromosomes (9%) were found among G0 versus 1257 per 3659 (34%) among G1-G4 TKO tumors. No significant differences in ploidy level were observed.  FIG. 2E  is a plot showing quantification of total number of cytogenetic aberrations detected by SKY in G0 (blue) and G1-G4 (red) thymic lymphomas. Darker color indicates proportion of events representing non-reciprocal translocations and lighter color indicates proportion representing dicentric/Robertsonian-like rearrangements.  FIG. 2F  is a recurrence plot of CNAs defined by array-CGH for 35 TKO lymphomas. X axis represents physical location of each chromosomes, and Y axis represents % of tumors exhibiting copy number alterations. The percentage of tumors harboring gains, amplifications, losses and deletions for each locus is depicted according to the following scheme: dark red (gains with a log 2 ratio=&gt;0.3) and green (loss with a log 2 ratio&lt;=−0.3) are plotted along with bright red (Amplifications with a log 2  ratio=&gt;0.6) and bright green (deletions with log 2  ratio&lt;=−0.6). Location of physiologically-relevant CNAs at Tcrβ, Tcrα/δ, and Tcrγ is indicated with arrows, and other loci discussed in the text (Notch1, Pten) are indicated by asterisks. 
           [0034]      FIG. 3 : Notch1 array-CGH and SKY.  FIG. 3A  shows a representative array-CGH Log 2 ratio plot from murine TKO lymphoma A1052 showing focal amplification targeting the 3′-end of Notch1 and its location relative to other genes in the region (http://genome.ucsc.edu/), NBCI mouse build 34. Y axis, log 2 ratio of copy number (normal set at log 2=0); amplifications are above and deletions are below this axis; X axis, chromosome position.  FIG. 3B  are SKY analyses of murine TKO tumors A1052 and A895 cells that harbor chromosome 2 amplifications which target the 3′ end of Notch1. Upper panels: metaphase spreads from the indicated tumors showing non-reciprocal translocations involving murine chromosome 2, marked by arrows; the asterisk indicates an abnormal band chr2A3. Lower panels: representative SKY images of individual rearranged chromosomes involving chromosome 2 and other chromosomes, as indicated. Each panel is a composite of raw spectral image (left), DAPI image (middle), and computer-interpreted spectral image (right) for the indicated rearranged chromosome.  FIG. 3C  shows breakpoint separating two contiguous BAC probes overlapping at Notch1, using FISH. Red signal, BAC probe RP24-369L23; green signal, BAC probe RP23-412O13. 
           [0035]      FIG. 4 . NOTCH1 alterations in both murine and human T-ALLs.  FIG. 4A  is a graphic illustration of Location of sequence alterations affecting Notch1 in murine TKO and human T-ALL tumors. Each marker is indicative of an individual cell line/patient.  FIG. 4B  shows Western blotting analysis of murine full-length Notch1 (FL; top), cleaved active Notch1 (V1744; middle), and tubulin loading control (bottom). High levels of activated Notch1 protein were expressed in many TKO tumors, including those harboring 3′ translocations (in blue: A577, A1052, A1252) and truncating deletion mutations (in red: A494, A1040), in which faster migrating V1744 forms are apparent. Human ALL-SIL (left) and normal mouse thymus (right) samples were loaded for controls.  FIG. 4C  shows that high levels of Notch1 mRNA correlate with high mRNA levels of known downstream targets of Notch1 protein, as assessed by expression profiling of TKO tumors. Each bar represents an individual probe set. Samples in blue lettering harbor 3′ translocations near Notch1; samples in red lettering harbor truncating deletion mutations, as indicated for  FIG. 4B . 
           [0036]      FIG. 5 . FBXW7 alterations are common in human T-ALL and conserved in the murine TKO tumors.  FIG. 5A  are a group of Log 2 ratio array-CGH plots showing conservation of CNAs resulting in deletion of FBXW7 in both mouse TKO and human T-ALL cell lines; the genomic location of Fbxw7 is indicated in green. Y axis, log 2 ratio of copy number (normal set at log 2=0); amplifications are above and deletions are below this axis; X axis, chromosome position.  FIG. 5B  shows relative expression level of mouse Fbxw7 mRNA, as assessed by real-time qPCR in the indicated murine TKO tumors.  FIG. 5C  is a graphic illustration of location of mutations in human FBXW7 identified in a panel of human T-ALL patients and cell lines. Each marker represents an individual cell line/patient. 
           [0037]      FIG. 6 : Focal deletion of Pten in TKO tumors.  FIG. 6A  is a representative array-CGH Log 2 ratio plot from a TKO lymphoma showing focal deletion encompassing Pten, and its location relative to other genes in the region (http://genome.ucsc.edu/, NBCI mouse build 34). Y axis, log 2 ratio of copy number (normal set at log 2=0); amplifications are above and deletions are below this axis; X axis, chromosome position.  FIG. 6B  summarizes the result of real-time qPCR (showing deletion in several tumors), with a graphic illustration of real-time qPCR with primer sets to the indicated regions (arrows) and the location of array-CGH 60-mer oligo probes (Agilent 44K array). A494 is shown as a control without evidence of deletion. 
           [0038]      FIG. 7 . Conservation of PTEN genetic alterations in human and mouse T-ALLs.  FIG. 7A  are a group of Log 2 ratio array-CGH plots demonstrating conservation of CNAs resulting in deletion of PTEN in both mouse TKO and human T-ALL cell lines; the genomic location of Pten is indicated in green. Y axis, log 2 ratio of copy number (normal set at log 2=0); amplifications are above and deletions are below this axis; X axis, chromosome position.  FIG. 7B  is a Western blotting analysis, showing the expression level of PTEN, phospho-Akt, and Akt in a panel of murine TKO and human T-ALL cell lines. BE13 and PEER are synonymous lines. Tubulin was probed simultaneously as a loading control. Samples in red harbor confirmed sequence mutations; samples in blue harbor aCGH-detected deletions.  FIG. 7C  are a group of Log 2 ratio array-CGH plots showing the effects of CNAs on other members of the Pten-Akt axis in murine TKO tumors. The location of each gene (Akt1, Tsc1) is shown in green. 
           [0039]      FIG. 8 : TKO cells with Pten mutation/deletion are sensitive to inhibition of phospho-Akt by the drug triciribine. Cells were plated in triplicate and exposed to the indicated doses of triciribine or vehicle alone for 48 hours and then quantified by MTS assay for viable cells. The fraction of surviving cells is plotted relative to survival in vehicle alone (set at 1). Tumor A1040 retains wildtype Pten expression and A1005 harbors a point mutation in one copy of Pten, whereas cell lines A577, A1240, A1252, and A494 are deficient for Pten expression. 
           [0040]      FIG. 9 . Substantial overlap between genomic alterations of murine TKO lymphomas and human tumors of diverse origins.  FIG. 9A  summarizes the result of statistical analysis of the cross-species overlap. We obtained Human array-CGH profiles from the indicated tumor types. We further defined MCRs as described in the Examples section (in particular, Example 4). Characteristics of each set are listed on the left portion of the panel. The number of TKO MCRs (amp, amplifications; del, deletions) with syntenic overlap with corresponding human CGH dataset is indicated on the right side of the panel, with p value for each based on 10,000 permutations.  FIG. 9B  are a group of Pie-chart representation of numbers of TKO MCRs (indicated within each segment) with syntenic overlap identified in one or multiple human tumor types (indicated by different colors of the segments); left, amplifications; right, deletions. For example, 21 of the 61 syntenic amplifications in  FIG. 9A  were observed in 2 different human tumor CGH datasets.  FIG. 9C  are a group of Venn diagram representation of the degree of overlap between murine TKO MCRs and MCRs from human cancers of T-ALL, multiple myeloma, or solid tumors (encompassing glioblastoma, melanoma, and pancreatic, lung, and colon adenocarcinoma). 
       
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
       [0041]    In vivo cancer models used for the discovery of cancer-related genes and therapeutic cancer targets typically produce cancer cells with benign chromosomal profiles, i.e., nearly normal chromosomal stability. In contrast, in naturally occurring human cancer, cancer cell genomes display widespread instability as evidenced by chromosomal structural aberrations. Accordingly, the present invention provides an in vivo cancer model with a destabilized genome (“genome unstable”). 
         [0042]    The genomes of cancer cells from the genome unstable model of the invention simulate the chromosomal instability displayed by human cancer cell genomes The genome unstable cancer model of the invention, thus, provides significant advantages for the discovery of genes and genetic elements involved in human cancer initiation, maintenance and progression. The chromosomal aberrations in cancer cells from the model, particularly recurrent aberrations, permit investigation of chromosomal events in cancer that is not possible in cancer models with “benign” chromosomal profiles. Such chromosomal aberrations also focus attention on particular regions of the genome more likely to harbor cancer-related elements. The validation herein of a genome unstable mouse cancer model that generates chromosomal and genetic events that mirror those in multiple types of human cancers provides an important new tool for the discovery of cancer-related genes and therapeutic targets of relevance to human cancer. Although useful by itself to discover genes and genetic elements relevant to human cancer, the genome unstable model of the invention also can be used as a background for establishing other cancer models, including known cancer models. Layering genetic modifications in known oncogenes and/or tumor suppressors onto the genome unstable model of the invention provides improved models that more closely replicate naturally occurring cancer. Even more importantly, the genome unstable model of the invention permits cross-species comparison with human cancer genomes to identify shared chromosomal and genetic events. Such shared events provide a powerful guide for the discovery of cancer-related genes and therapeutic targets. 
       1. DEFINITIONS 
       [0043]    Throughout this specification and embodiments, the word “comprise” or variations such as “comprises” or “comprising” will be understood to imply the inclusion of a stated integer or group of integers but not the exclusion of any other integer or group of integers. 
         [0044]    Unless otherwise defined herein, scientific and technical terms used in connection with the present invention shall have the meanings that are commonly understood by those of ordinary skill in the art. Further, unless otherwise required by context, singular terms shall include pluralities and plural terms shall include the singular. Generally, nomenclatures used in connection with, and techniques of, cell and tissue culture, molecular biology, cell and cancer biology, virology, immunology, microbiology, genetics and protein and nucleic acid chemistry described herein are those well known and commonly used in the art. 
       2. ANIMAL MODELS 
       [0045]    Most standard genetically engineered mouse models of cancer have relatively benign cytogenetic profiles. These genomically stable models do not reflect the widespread chromosomal instability that is typical of human genomes in cancer. It has been reported that in most “genome-stable” murine tumor models, about 20 to 40 chromosomal aberrations were detected per genome, or, less than 0.1 chromosomal rearrangements per chromosome. 
         [0046]    Accordingly, in one aspect, the invention provides a non-human animal that is genetically modified to develop cancer, wherein the genomes of cancer cells from the animal display enhanced chromosomal instability as evidenced by a frequency of chromosomal structural aberration that approaches or matches that seen in human cancer cells. In various embodiments, the frequency of chromosomal structural aberrations in a population of cancer cells from the non-human animal model is at least 1.5-fold, 2-fold, 3-fold, 4-fold, 5-fold or 10-fold higher than the frequency of chromosomal structural aberrations in such mammal without the genetic modification, whether defined on a per-genome or per-chromosome basis. 
         [0047]    The frequency of chromosomal abnormalities can be based on the average number of such abnormalities per genome or per chromosome, or the average number of a particular type of chromosomal abnormality per genome, or the average number of aberrations in a particular chromosome. Methods of measuring chromosomal alterations are known in the art (see, e.g., R. C. O&#39;Hagan, et al., Cancer Res 63 (17), 5352 (2003); N. Bardeesy, et al., Proc Natl Acad Sci USA 103 (15), 5947 (2006); M. Kim, et al., Cell 125 (7), 1269 (2006); L. Zender, et al., Cell 125 (7), 1253 (2006)), and are further disclosed below. Cancer cells from the genome unstable non-human animal model of the invention will have an enhanced frequency of chromosomal aberrations compared to cells derived from comparable non-human animal models lacking the genome destabilizing mechanisms described above, by at least one of the aforementioned parameters. 
         [0048]    A chromosomal structural aberration may be any chromosomal abnormality resulting from DNA gains or losses, DNA amplification, DNA deletion, and DNA translocation. Exemplary chromosomal structural aberrations include, for example, sister chromatid exchanges, multi-centric chromosomes, inversions, gains, losses, reciprocal and non-reciprocal translocations (NRTs), p-p robertsonian-like translocations of homologous and/or non-homologous chromosomes, p-q chromosome arm fusions, and q-q chromosome arm fusions. 
         [0049]    The genetic modifications in the genome unstable animal model of the invention can be in any gene or genetic element that renders the animal cancer-prone and affects genome structure or genome stability, so that the modifications destabilize the genome, as evidenced by an increased frequency of chromosomal structural aberrations in the genomes and/or chromosomes of cancer that develops in the animal compared to genomes and/or chromosomes in comparable animal models lacking such genome destabilizing mechanisms. Genetic elements include [DNA that is not translated to produce a protein product such as micro RNA, expression control sequences including DNA transcription factor binding sites, RNA transcription initiation sites, promoters, enhancers, response elements and the like. In some embodiments the genetic modifications inactivate a gene or genetic element involved in chromosomal structural stability or integrity. Inactivation may be by directly inactivating the gene or genetic element, by suppressing the expression, or by inactivating or inhibiting the activity of a gene product, which can be a nucleic acid product including RNA or a protein gene product 
         [0050]    In some embodiments, the genetic modifications comprise inactivation of at least one allele of one or more genes or genetic elements involved in DNA repair and inactivation of at least one allele of one or more genes or genetic elements involved in a DNA damage checkpoint. In some embodiments, the genetic modifications further comprise inactivation of at least one allele of a gene or genetic element involved in telomere maintenance. In any of the foregoing embodiments, both alleles of the DNA repair related, DNA damage checkpoint related and/or telomere maintenance related genes or genetic elements may be inactivated. 
         [0051]    Any gene or genetic element involved in DNA repair or in a DNA damage checkpoint can be inactivated in the genome unstable model of the invention. Many such genes and genetic elements in humans an other mammals will be known to those of skill in the art. See, for example, R. D. Wood et al., Human DNA Repair Genes,  Science,  291: 1284-1289 (February 2001); R A Bulman, S D Bouffler, R Cox and T A Dragani, Locations of DNA Damage Response and Repair Genes in the Mouse and Correlation with Cancer Risk Modifiers, National Radiological Protection Board Report, October 2004 (ISBN 0-85951-544-3). The mouse DNA repair gene database is available at the UK Health Protection Agency website. 
         [0052]    They include, for example, genes encoding base excision repair (BER) proteins such as ung, smug1, mbd4, tdg, off1, myh, nth1, mpg, ape1, ape2, lig3, xrcc1, adprt, adprtl2 and adprtl3 or species homologs thereof; mismatch excision repair proteins such as msh2, msh3, msh4, msh5, msh6, pms1, pms3, mlh1, mlh3, pms2l3 and pms2l4 or species homologs thereof; nucleotide excision repair (NER) proteins, non-homologous end joining (NHEJ) proteins, homologous recombination proteins, DNA polymerases, editing and processing nucleases and DNA repair helicases, among others. Wood et al., supra. 
         [0053]    Exemplary NHEJ proteins include Ligase4, XRCC4, H2AX, DNAPKcs, Ku70, Ku80, Artemis, Cernunnos/XLF, MRE11, NBS1, and RAD50. Exemplary homologous recombination proteins include RAD51, RAD52, RAD54, XRCC3, RAD51C, BRCA1, BRCA2 (FANCD1), FANCA, FANCB, FANCC, FANCD2; FANCE, FANCF, FANCG, FANCJ (BRIP1/BACH1), FANCL, and FANCM. Exemplary DNA repair helicases include BLM and WRN. 
         [0054]    Any gene or genetic element involved in a DNA damage checkpoint can be used in the genome unstable model of the invention. Information about many such genes and genetic elements is readily available and will be well-known those of skill in the art. Exemplary DNA checkpoint proteins include sensor proteins such as RAD1, RAD9, RAD17, HUS1, MRE11, Rad50, and NBS1; mediators such as ATRIP; phosphoinositide 3-kinase related kinase (PIKK) family proteins such as ATM, ATR, SMG-1 and DNA-PK; checkpoint kinases such as Chk1 and Chk2; and effector proteins such as p53, p63, p73, CDC25A, B and C, p21 and 14-3-3β,γ,ξ,σ,ε,η,τ APC; BRCA1, MDM2, MDM4, NBS1, RAD24, RAD 25, RAD50, MDC1, SMC1, and claspin. 
         [0055]    In one embodiment of the genome unstable model of the invention, the non-human transgenic animal further comprises engineered inaction of at least one allele of one or more genes or genetic elements involved in synthesizing or maintaining telomere length. In some embodiments, the non-human transgenic mammal is engineered for decreased telomerase activity, for example by inactivation of telomerase reverse transcriptase, Tert, or telomerase RNA (Terc). In some embodiments the genetic modification decreases the activity of a protein affecting telomere structure such as capping function. Exemplary proteins that affect telomere structure include TRF1, TRF2, POT1a, POT1b, RAP1, TIN2, and TPP1. 
         [0056]    The non-human genome unstable model of the invention may be any animal, including, fish, birds, mammals, reptiles, amphibians. Preferably, the animal is a mammal, including rodents, primates, cats, dogs, goats, horses, sheep, pigs, cows. In preferred embodiments, the mammal is a mouse. 
         [0057]    The genome unstable animal models of the invention include animals in which all or only some portion of cells comprise the genetic modifications that create genome instability. In some embodiments, the germ cells of the animal comprise the genetic modifications. 
         [0058]    In some embodiments, the genome unstable model comprises inactivation of one or both alleles of atm, terc or p53 or any combination of those genes. In a particular embodiment, one or both alleles of all three genes are inactivated. In some embodiments both alleles of atm are inactivated. In a particular embodiment, both alleles of all three genes are inactivated. 
         [0059]    Also within the invention are tissues and cells from the genome unstable model of the invention, including somatic cells, germ cells, stem cells including embryonic stem cells, differentiated cells and undifferentiated cells. The cells may be cancer cells, non-cancer cells, or pre-cancer cells. 
         [0060]    Inactivation of a gene or a genetic element in the genome unstable animal model of the invention can be achieved by any means, many of which are well-known to those of skill in the art. Such means include deletion of all or part of the gene or genetic element or introducing an inactivating mutation (lesion) in the gene or genetic element. Deletion of all or a portion of a gene or genetic element may be by knock-out such as by homologous recombination or techniques using Cre recombinase (e.g., a Cre-Lox system). Deletions including knock-outs can be conditional knock-outs, where alteration of a nucleic acid sequences can occur upon, for example, exposure of the animal to a substance that promotes gene alteration, introduction of an enzyme that promotes recombination at the gene site (e.g., Cre in the Cre-lox system), or other method for directing the gene alteration. Conditional or constitutive knock-outs can be tissue-specific, temporally-specific (e.g., occurring during a particular developmental stage) or both. 
         [0061]    Inactivating mutations may be introduced using any means, many of which are well known. Such methods include site directed mutagenesis for example using homologous recombination or PCR. Such mutations may be introduced in the 5′ untranslated region (UTR) of a gene, including in an expression control region, in a coding region (intron or exon) or in the 3′ UTR. 
         [0062]    The expression or activity of a gene or genetic element also may be accomplished by any means including but not limited to RNA interference, antisense including triple helix formation and ribozymes including RNaseP, leadzymes, hairpin ribozymes and hammerhead ribozymes. 
         [0063]    In some embodiments, the genome unstable animal model of the invention further comprises one or more additional cancer-promoting genetic modifications including but not limited to the introduction of one or more activated oncogenes, modifications to increase the expression of one or more oncogenes, targeted inactivation of one or more tumor-suppressors, or combinations of the foregoing. Such additional cancer-promoting modifications may be inducible, tissue specific, temporally specific or any combination of the three. For example, an oncogene can be introduced into the genome using an expression cassette that includes in the 5′-3′ direction of transcription, a transcriptional and translational initiation region that is associated with gene expression in a specific tissue type, an oncogene, and a transcriptional and translational termination region functional in the host animal. One or more introns may also be present. In addition to the oncogene of interest, a detectable marker, such as GFP (and its variants), luciferase, and lacZ may be optionally operably linked to the oncogene and co-expressed. Similarly, a tumor-suppressor-gene may be inactivated using, for example, gene targeting technology. 
         [0064]    Introducing additional cancer-promoting modifications into a genome-unstable animal model described herein creates a powerful tool for cancer gene discovery. For example, Kras activation and p53 mutation in pancreas are known to cause pancreas cancer in human. A genome-unstable model having pancreas-specific Kras activation, p53 inactivation (and optionally, a decreased telomere function) would greatly facilitate the discovery of pancreas cancer gene in human. 
         [0065]    The cancer in the genome unstable model any type of cancer, including carcinoma, sarcoma, myeloma, leukemia, lymphoma or mixed cancer types. The cancer can arise from any tissue type including epithelial tissue, mesenchymal tissue, nervous tissue and hematopoietic tissue and be located in any organ or tissue of the body. The frequency of chromosomal aberrations can be determined in cells from any of the aforementioned cancers and can be from a primary tumor, a secondary tumor, a metastatic tumor, a tumor recurrence perhaps normal cells derived from said genomically unstable model that were genetically manipulated in vitro, through additional oncogene activation and tumor suppressor gene inactivation introduced by those knowledgeable in the art, to become cancerous 
         [0066]    The genome unstable mouse model of the invention may develop any cancer including but not limited to acral lentiginous melanoma, actinic keratoses, adenocarcinoma, adenoid cystic carcinoma, adenomas, adenosarcoma, adenosquamous carcinoma, adrenocortical carcinoma, AIDS-related lymphoma, anal cancer, anaplastic glioma, astrocytic tumors, astrocytomas, bartholin gland carcinoma, basal cell carcinoma, biliary tract cancer, bone cancer, bile duct cancer, bladder cancer, brain stem glioma, brain tumors, breast cancer, bronchial gland carcinomas, capillary carcinoma, carcinoids, carcinoma, carcinosarcoma, cavernous, central nervous system lymphoma, cerebral astrocytoma, cervical cancer, connective tissue cancer, cholangiocarcinoma, chondosarcoma, choroid plexus papilloma/carcinoma, clear cell carcinoma, colon cancer, colorectal cancer, cutaneous T-cell lymphoma, cystadenoma, endodermal sinus tumor, endometrial hyperplasia, endometrial stromal sarcoma, endometrioid adenocarcinoma, ependymal, ependymoma, epitheloid, esophageal cancer, Ewing&#39;s sarcoma, extragonadal germ cell tumor, eye cancer, fibrolamellar, focal nodular hyperplasia, gallbladder cancer, gangliogliomas, gastric cancer, gastrinoma, germ cell tumors, gestational trophoblastic tumor, glioblastoma multiforme, glioma, glucagonoma, head and neck cancer, hemangiblastomas, hemangioendothelioma, hemangiomas, hepatic adenoma, hepatic adenomatosis, hepatocellular carcinoma, Hodgkin&#39;s lymphoma, hypopharyngeal cancer, hypothalamic and visual pathway glioma, childhood, insulinoma, intaepithelial neoplasia, interepithelial squamous cell neoplasia, intraocular melanoma, intra-epithelial neoplasm, invasive squamous cell carcinoma, large cell carcinoma, islet cell carcinoma, Kaposi&#39;s sarcoma, kidney cancer, laryngeal cancer, leiomyosarcoma, lentigo maligna melanomas, leukemia-related disorders, lip and oral cavity cancer, liver cancer, lung cancer, lymphoma, malignant mesothelial tumors, malignant thymoma, medulloblastoma, medulloepithelioma, melanoma, meningeal, merkel cell carcinoma, mesothelial, metastatic carcinoma, mucoepidermoid carcinoma, multiple myeloma/plasma cell neoplasm, mycosis fungoides, myelodysplastic syndrome, myeloproliferative disorders, nasal cavity and paranasal sinus cancer, nasopharyngeal cancer, neuroblastoma, neurofibromatosis, neuroepithelial adenocarcinoma nodular melanoma, non-Hodgkin&#39;s lymphoma, non-small cell lung cancer, oat cell carcinoma, oligodendroglial, oligoastrocytomas, oral cancer, oropharyngeal cancer, osteosarcoma, pancreatic polypeptide, ovarian cancer, ovarian germ cell tumor, pancreatic cancer, papillary serous adenocarcinoma, pineal cell, pituitary tumors, plasmacytoma, pseudosarcoma, pulmonary blastoma, parathyroid cancer, penile cancer, pheochromocytoma, pineal and supratentorial primitive neuroectodermal tumors, pituitary tumor, plasma cell neoplasm, pleuropulmonary blastoma, prostate cancer, rectal cancer, renal cell carcinoma, cancer of the respiratory system, retinoblastoma, rhabdomyosarcoma, sarcoma, serous carcinoma, skin cancer, small cell carcinoma, small intestine cancer, soft tissue carcinomas, somatostatin-secreting tumor, squamous carcinoma, squamous cell carcinoma, stomach cancer, stromal tumors, submesothelial, superficial spreading melanoma, supratentorial primitive neuroectodermal tumors, testicular cancer, thyroid cancer, undifferentiatied carcinoma, urethral cancer, uterine sarcoma, uveal melanoma, verrucous carcinoma, vaginal cancer, vipoma, vulvar cancer, Waldenstrom&#39;s macroglobulinemia, well differentiated carcinoma, and Wilm&#39;s tumor. 
         [0067]    The animal models described herein are typically obtained using transgenic technologies. Transgenic technologies are well known in the art. For example, transgenic mouse can be prepared in a number of ways. A exemplary method for making the subject transgenic animals is by zygote injection. This method is described, for example in U.S. Pat. No. 4,736,866. The method involves injecting DNA into a fertilized egg, or zygote, and then allowing the egg to develop in a pseudo-pregnant mother. The zygote can be obtained using male and female animals of the same strain or from male and female animals of different strains. The transgenic animal that is born is called a founder, and it is bred to produce more animals with the same DNA insertion. In this method of making transgenic animals, the exogenous DNA typically randomly integrates into the genome by a non-homologous recombination event. One to many thousands of copies of the DNA may integrate at one site in the genome. 
       3. METHODS OF IDENTIFYING CANCER-RELATED GENES 
       [0068]    In another aspect, the invention provides methods for identifying genes and genetic elements involved in cancer initiation, maintenance and/or progression in humans utilizing the genome unstable model of the invention. The gene discovery and identification methods are based on the surprising discovery described herein that chromosomal structural aberrations, copy number alterations and mutations in cancer cells in a genome unstable mouse model have syntenic counterparts (i.e., occurring in evolutionarily related chromosomal regions) in human cancer cells. 
         [0069]    Accordingly, in one embodiment, the invention provides a method of identifying a chromosomal region of interest for the identification of a gene that is potentially related to human cancer, comprising the step of identifying a DNA copy number alteration in a population of cancer cells from a non-human, genome-unstable mammal described above. The chromosomal region where the DNA copy number alteration occurred is a chromosomal region of interest for the identification of a gene or genetic element (such as microRNAs) that is potentially related to human cancer. 
         [0070]    A DNA copy number alteration may be a DNA gain (such as amplification of a genomic region) or a DNA loss (such as deletion of a genomic region). Methods of evaluating the copy number of a particular genomic region are well known in the art, and include, hybridization and amplification based assays. According to the methods of the invention, DNA copy number alterations may be identified using copy number profiling, such as comparative genomic hybridization (CGH) (including both dual channel hybridization profiling and single channel hybridization profiling (e.g. SNP-CGH)). Other suitable methods including fluorescent in situ hybridization (FISH), PCR, nucleic acid sequencing, and loss of heterozygosity (LOH) analysis may be used in accordance with the invention. 
         [0071]    In one embodiment of the invention, the DNA copy number alterations in a genome are determined by copy number profiling. 
         [0072]    In some embodiments of the invention, the DNA copy number alterations are identified using CGH. In comparative genomic hybridization methods, a “test” collection of nucleic acids (e.g. from a tumor or cancerous cells) is labeled with a first label, while a second collection (e.g. from a normal cell or tissue) is labeled with a second label. The ratio of hybridization of the nucleic acids is determined by the ratio of the first and second labels binding to each fiber in an array. Differences in the ratio of the signals from the two labels, for example, due to gene amplification in the test collection, is detected and the ratio provides a measure of the gene copy number, corresponding to the specific probe used. A cytogenetic representation of DNA copy-number variation can be generated by CGH, which provides fluorescence ratios along the length of chromosomes from differentially labeled test and reference genomic DNAs. 
         [0073]    In some embodiments of the present invention, the DNA copy number alterations are analyzed by microarray-based CGH (array-CGH). Microarray technology offers high resolution. For example, the traditional CGH generally has a 20 Mb limited mapping resolution; whereas in microarray-based CGH, the fluorescence ratios of the differentially labeled test and reference genomic DNAs provide a locus-by-locus measure of DNA copy-number variation, thereby achieving increased mapping resolution. Details of various microarray methods can be found in the literature. See, for example, U.S. Pat. No. 6,232,068; Pollack et al., Nat. Genet., 23(1):41-6, (1999), Pastinen (1997) Genome Res. 7: 606-614; Jackson (1996) Nature Biotechnology 14:1685; Chee (1995) Science 274: 610; WO 96/17958, Pinkel et al. (1998) Nature Genetics 20: 207-211 and others. 
         [0074]    The DNA used to prepare the CGH arrays is not critical. For example, the arrays can include genomic DNA, e.g. overlapping clones that provide a high resolution scan of a portion of the genome containing the desired gene or of the gene itself. Genomic nucleic acids can be obtained from, e.g., HACs, MACs, YACs, BACs, PACs, PIs, cosmids, plasmids, inter-Alu PCR products of genomic clones, restriction digests of genomic clones, cDNA clones, amplification (e.g., PCR) products, and the like. Arrays can also be obtained using oligonucleotide synthesis technology. For example, see, e.g., light-directed combinatorial synthesis of high density oligonucleotide arrays U.S. Pat. No. 5,143,854 and PCT Patent Publication Nos. WO 90/15070 and WO 92/10092. 
         [0075]    The sensitivity of the hybridization assays may be enhanced through use of a nucleic acid amplification system that multiplies the target nucleic acid being detected. Examples of such systems include the polymerase chain reaction (PCR) system and the ligase chain reaction (LCR) system. Other suitable methods include are the nucleic acid sequence based amplification (NASBAO, Cangene, Mississauga, Ontario) and Q Beta Replicase systems. 
         [0076]    In one embodiment of the invention, the DNA copy number alterations in a genome are determined by single channel profiling, such as single nucleotide polymorphism (SNP)-CGH. Traditional CGH data consists of two channel intensity data corresponding to the two alleles. The comparison of normalized intensities between a reference and subject sample is the foundation of traditional array-CGH. Single channel profiling (such as SNP-CGH) is different in that a combination of two genotyping parameters are analyzed: normalized intensity measurement and allelic ratio. Collectively, these parameters provide a more sensitive and precise profile of chromosomal aberrations. SNP-CGH also provides genetic information (haplotypes) of the locus undergoing aberration. Importantly, SNP-CGH has the capability of identifying copy-neutral LOH events, such as gene conversion, which cannot be detected with array-CGH. 
         [0077]    In another embodiment, FISH is used to determine the DNA copy number alterations in a genome. Fluorescence in situ hybridization (FISH) is known to those of skill in the art (see Angerer, 1987 Meth. Enzymol., 152: 649). Generally, in situ hybridization comprises the following major steps: (1) fixation of tissue or biological structure to be analyzed; (2) prehybridization treatment of the biological structure to increase accessibility of target DNA, and to reduce nonspecific binding; (3) hybridization of the mixture of nucleic acids to the nucleic acid in the biological structure or tissue; (4) post-hybridization washes to remove nucleic acid fragments not bound in the hybridization, and (5) detection of the hybridized nucleic acid fragments. 
         [0078]    In a typical in situ hybridization assay, cells or tissue sections are fixed to a solid support, typically a glass slide. If a nucleic acid is to be probed, the cells are typically denatured with heat or alkali. The cells are then contacted with a hybridization solution at a moderate temperature to permit annealing of labeled probes specific to the nucleic acid sequence encoding the protein. The targets (e.g., cells) are then typically washed at a predetermined stringency or at an increasing stringency until an appropriate signal to noise ratio is obtained. 
         [0079]    The probes used in such applications are typically labeled, for example, with radioisotopes or fluorescent reporters. Preferred probes are sufficiently long, for example, from about 50, 100, or 200 nucleotides to about 1000 or more nucleotides, to enable specific hybridization with the target nucleic acid(s) under stringent conditions. 
         [0080]    In some applications it is necessary to block the hybridization capacity of repetitive sequences. Thus, in some embodiments, tRNA, human genomic DNA, or Cot-1 DNA is used to block non-specific hybridization. 
         [0081]    In another embodiment, Southern blotting is used to determine the DNA copy number alterations in a genome. Methods for doing Southern blotting are known to those of skill in the art (see Current Protocols in Molecular Biology, Chapter 19, Ausubel, et al., Eds., Greene Publishing and Wiley-Interscience, New York, 1995, or Sambrook et al., Molecular Cloning: A Laboratory Manual, 2d Ed. vol. 1-3, Cold Spring Harbor Press, NY, 1989). In such an assay, the genomic DNA (typically fragmented and separated on an electrophoretic gel) is hybridized to a probe specific for the target region. Comparison of the intensity of the hybridization signal from the probe for the target region with control probe signal from analysis of normal genomic DNA (e.g., genomic DNA from the same or related cell, tissue, organ, etc.) provides an estimate of the relative copy number of the target nucleic acid. 
         [0082]    In one embodiment, amplification-based assays, such as PCR, are used to determine the DNA copy number alterations in a genome. In such amplification-based assays, the genomic region where a copy number alteration occurred serves as a template in an amplification reaction. In a quantitative amplification, the amount of amplification product will be proportional to the amount of template in the original sample. Comparison to appropriate controls provides a measure of the copy number of the genomic region. 
         [0083]    Methods of “quantitative” amplification are well known to those of skill in the art. For example, quantitative PCR involves simultaneously co-amplifying a known quantity of a control sequence using the same primers. This provides an internal standard that may be used to calibrate the PCR reaction. Detailed protocols for quantitative PCR are provided, for example, in Innis et al. (1990) PCR Protocols, A Guide to Methods and Applications, Academic Press, Inc. N.Y. 
         [0084]    Real time PCR can be used in the methods of the invention to determine DNA copy number alterations. (See, e.g., Gibson et al., Genome Research 6:995-1001, 1996; Heid et al., Genome Research 6:986-994, 1996). Real-time PCR evaluates the level of PCR product accumulation during amplification. To measure DNA copy number, total genomic DNA is isolated from a sample. Real-time PCR can be performed, for example, using a Perkin Elmer/Applied Biosystems (Foster City, Calif.) 7700 Prism instrument. Matching primers and fluorescent probes can be designed for genes of interest using, for example, the primer express program provided by Perkin Elmer/Applied Biosystems (Foster City, Calif.). Optimal concentrations of primers and probes can be initially determined by those of ordinary skill in the art, and control (for example, beta-actin) primers and probes may be obtained commercially from, for example, Perkin Elmer/Applied Biosystems (Foster City, Calif.). To quantitate the amount of the specific nucleic acid of interest in a sample, a standard curve is generated using a control. Standard curves may be generated using the Ct values determined in the real-time PCR, which are related to the initial concentration of the nucleic acid of interest used in the assay. Standard dilutions ranging from 10-10 6  copies of the gene of interest are generally sufficient. In addition, a standard curve is generated for the control sequence. This permits standardization of initial content of the nucleic acid of interest in a tissue sample to the amount of control for comparison purposes. 
         [0085]    Methods of real-time quantitative PCR using TaqMan probes are well known in the art. Detailed protocols for real-time quantitative PCR are provided, for example, for RNA in: Gibson et al., 1996, A novel method for real time quantitative RT-PCR. Genome Res., 10:995-1001; and for DNA in: Heid et al., 1996, Real time quantitative PCR. Genome Res., 10:986-994. 
         [0086]    A TaqMan-based assay also can be used to quantify a particular genomic region for DNA copy number alterations. TaqMan based assays use a fluorogenic oligonucleotide probe that contains a 5′ fluorescent dye and a 3′ quenching agent. The probe hybridizes to a PCR product, but cannot itself be extended due to a blocking agent at the 3′ end. When the PCR product is amplified in subsequent cycles, the 5′ nuclease activity of the polymerase, for example, AmpliTaq, results in the cleavage of the TaqMan probe. This cleavage separates the 5′ fluorescent dye and the 3′ quenching agent, thereby resulting in an increase in fluorescence as a function of amplification (see, for example, http://www2.perkin-elmer.com). 
         [0087]    Other suitable amplification methods include, but are not limited to ligase chain reaction (LCR) (see Wu and Wallace (1989) Genomics 4:560, Landegren et al. (1988) Science 241:1077, and Barringer et al. (1990) Gene 89:117), transcription amplification (Kwoh et al. (1989) Proc. Natl. Acad. Sci. USA 86:1173), self-sustained sequence replication (Guatelli et al. (1990) Proc. Nat. Acad. Sci. USA 87:1874), dot PCR, and linker adapter PCR, etc. 
         [0088]    In one embodiment, DNA sequencing is used to determine the DNA copy number alterations in a genome. Methods for DNA sequencing are known to those of skill in the art. 
         [0089]    In one embodiment, karyotyping (such as spectral karyotyping, SKY) is used to determine the chromosomal structural aberrations in a genome. Methods for karyotyping are known to those of skill in the art. For example, for SKY, a collection of DNA probes, each complementary to a unique region of one chromosome, may be prepared and labeled with a fluorescent color that is designated for a specific chromosome. DNA amplification, deletion, translocations or other structural abnormalities may be determined based on fluorescence emission of the probes. 
         [0090]    In certain embodiments, tumor samples from two or more genome-unstable animal models of the invention are analyzed for DNA copy number alterations, and the common genomic regions where the copy number alterations occurred in at least two of the samples are identified. Such recurrent DNA copy number alterations are of particular interest. 
         [0091]    A minimum common region (MCR) of the recurrent DNA copy number alteration may be defined when copy number alterations of two or more samples are compared. In one embodiment, the MCR is defined by the boundaries of overlap between two samples, or by boundaries of a single tumor against a background of larger alterations in at least one other tumor. 
         [0092]    Methods for determining MCRs is known in the art (see, e.g., D. R. Carrasco, et al.,  Cancer Cell  9 (4), 313 (2006); A. J. Aguirre, et al.,  Proc Natl Acad Sci USA  101 (24), 9067 (2004)). Briefly, a “segmented” dataset was generated by determining uniform copy number segment boundaries and then replacing raw log 2 ratio for each probe by the mean log 2 ratio of the segment containing the probe. A threshold representing minimal copy number alterations (CNAs) is then chosen to filter out noise. For example, the median log 2 ratio of a two-fold change for the platform may be chosen as a threshold. In an exemplary embodiment, the thresholds representing CNAs are +/−0.6 (Agilent 22K a-CGH platform) and +/−0.8 (Agilent 44K/244K a-CGH platform), and the width of MCR is less than 10 Mb. 
         [0093]    The boundaries of MCRs can be mapped by any method that is known in the art, such as southern blotting, or PCR. 
         [0094]    Genes and genetic elements located within an MCR are potentially related to human cancer and such genes and genetic elements can be subject to additional analyses to further characterize them. For example, a gene that is initially identified by array-CGH may be quantitatively amplified. Quantitative amplification of either the identified genomic DNA or the corresponding RNA can confirm DNA gain or loss. Alternatively, if the sequence encodes a protein, the mRNA level, protein level, or activity level of the encoded protein may be measured. An increase in RNA/protein/activity level, as compared to a control, confirms DNA amplification; a decrease in RNA/protein/activity level, as compared to a control, confirms DNA deletion. 
         [0095]    The gene or genetic element identified through initial screening may also be re-sequenced to confirm amplification or deletion. Further, DNA sequencing and protein expression profiling may also be used to identify genetic mutations that may be associated with tumorigenesis. 
         [0096]    In another aspect, the invention provides a method of identifying a chromosomal region of interest for the identification of a gene or genetic element that is potentially related to human cancer, comprising the step of identifying a chromosomal structural aberration in a population of cancer cells from a genome-unstable animal models of the invention. A chromosomal region containing the chromosomal structural aberration is a chromosomal region of interest for the identification of a gene or genetic element that is potentially related to human cancer. 
         [0097]    In some embodiments, the chromosomal structural aberration is detected using karyotyping, such as SKY. In some embodiments, the method further comprises determining the DNA copy number alteration, as described above. A chromosomal region containing the both chromosomal structural aberration and a DNA copy number alteration is a chromosomal region of interest for the identification of a gene or genetic element that is potentially related to human cancer. 
         [0098]    In another aspect, the invention provides a method of identifying a potential human cancer-related gene or genetic element, comprising the steps of (a) identifying a chromosomal region of interest as described herein; (b) identifying a gene or a genetic element within the chromosomal region of interest in the non-human animal, and (c) identifying a human gene or genetic element that corresponds to the gene or genetic element identified in step (b). 
         [0099]    Additionally, many public and private databases provide cancer gene information (for example, Sanger&#39;s Cancer Gene Census, at http://www.sanger.ac.uk/genetics/CGP/Census), and the information may be used to map known cancer genes to a particular chromosomal region. 
         [0100]    If a gene or a genetic element is found to be potentially relevant to human cancer, the corresponding human gene may be identified by homolog mapping, ortholog mapping, paralog mapping, among other methods. As used herein, a homolog is a gene related to a second gene by descent from a common ancestral DNA sequence, an ortholog is a gene in a different species that evolved from a common ancestral gene by speciation, and a paralogs is a gene related by duplication within a genome. 
         [0101]    In one embodiment, human homologs are identified by using, for example, the NCBI homologene website, http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=homologene. 
         [0102]    In some embodiments, the method further comprises detecting a mutation in the identified non-human gene or genetic element. In another embodiment, a mutation in the corresponding human gene or genetic element is identified. In another embodiment, mutations in the both the non-human gene or genetic element and the human gene or genetic element are identified, and the mutations are compared. 
         [0103]    In another aspect, the invention provides a method of identifying a potential human cancer-related gene or genetic element, comprising the steps of (a) detecting a DNA copy number alteration in a population of cancer cells from a non-human mammal, wherein the genome of the non-human mammal is engineered to produce genome instability, (b) identifying a gene or genetic element located within the boundaries of the copy number alteration detected in step (a), (c) identifying a human gene or genetic element that corresponds to the gene or genetic element identified in step (b) and that is located within the boundaries of a copy number alteration or of a chromosomal structural aberration in a human cancer cell. The human gene or genetic element identified in step (c) is a gene potentially related to human cancer. 
         [0104]    Methods for detecting a copy number alteration or a chromosomal structural aberration have been described above in detail. Methods for identifying a gene or genetic element located within the boundaries of the copy number alteration are also described above in detail. 
         [0105]    In one embodiment, a copy number alteration or a chromosomal structure aberration in the non-human animal model of the invention is compared with a copy number alteration or a chromosomal structural aberration in human cancer cell. A potentially relevant human cancer related gene or genetic element is identified based on synteny. Synteny describes the preserved order and orientation of genes between related species. Comparisons of non-human animal model and human cancer syntenic chromosomal regions may reveal the conserved nature of certain genetic modification in tumorgenesis. 
         [0106]    The cross-species comparison based on synteny has several advantages. First is the ability to narrow the chromosomal regions of interest—certain genomic modification is more focal in one species than the other, and a cross-species comparison may eliminate such species-specific event. Second, a minimal common region (MCR) typically contains a number of genes; a cross-species comparison of syntenic regions allows an efficient way to reduce the gene numbers because the syntenic regions of the genome between non-human mammals (in particular, mice) and humans may be in relatively small portions. Genes located within syntenic MCRs may be highly relevant to human cancers. 
         [0107]    In another aspect, the invention provides a method of identifying a potential human cancer-related gene or genetic element, comprising the steps of (a) detecting a chromosomal structural aberration in a population of cancer cells from a non-human mammal, wherein the genome of the non-human mammal is engineered to produce genome instability, (b) identifying a gene or genetic element located within the boundaries of the copy number alteration detected in step (a), (c) identifying a human gene or genetic element that corresponds to the gene or genetic element identified in step (b) and that is located within the boundaries of a copy number alteration or of a chromosomal structural aberration in a human cancer cell. The human gene or genetic element identified in step (c) is a gene potentially related to human cancer. 
       4. DIAGNOSIS AND METHODS OF TREATMENT 
       [0108]    In one aspect, the present invention provides a method for identifying subjects with T-cell acute lymphoblastic leukemia (T-ALL) who may have a decreased or increased response to γ-secretase inhibitor therapy, based on the discovery that inactivation of FBXW7 is associated with human T-cell malignancy. 
         [0109]    In one embodiment, the method for identifying subjects with T-ALL who may have a decreased response to a γ-secretase inhibitor therapy comprises: detecting in a cancer cell from the subject the expression level or activity level of FBXW7; a decreased expression/activity of FBXW7, as compared to a control, indicates that the subject may have a decreased response to a γ-secretase inhibitor therapy. The expression or activity level of NOTCH1 in the cancer cell may also be determined simultaneously; an increased expression/activity of NOTCH1, as compared to a control, further indicates that the subject may have a decreased response to a γ-secretase inhibitor therapy. Conversely, an increased expression/activity of FBXW7 (together with a decreased expression/activity of NOTCH1, optionally), as compared to a control, indicates that the subject may be sensitive to a γ-secretase inhibitor therapy. 
         [0110]    γ-Secretase is a complex composed of at least four proteins, namely presenilins (presenilin 1 or -2), nicastrin, PEN-2, and APH-1. Several proteins have been identified as substrates for γ-secretase cleavage, include Notch and the Notch ligands Delta1 and Jagged2, ErbB4, CD44, and E-cadherin (Wong, G. T. et. al, J. Biol. Chem., Vol. 279, Issue 13, 12876-12882, Mar. 26, 2004). The cleavage of Notch by γ-secretase has been studied most extensively. Notch plays an evolutionarily conserved role in regulating cell growth and lineage specification particularly during embryonic development. Notch is activated by several ligands (Delta, Jagged, and Serrate) and is then proteolytically processed by a series of ligand-dependent and -independent cleavages. γ-Secretase catalyzes the terminal cleavage event (S3 cleavage), which releases a fragment known as the Notch intracellular domain (NICD). The NICD fragment then translocates to the nucleus where it acts as a nuclear transcription factor. As expected from its role in Notch S3 cleavage, γ-secretase inhibitors have been shown to block NICD production in vitro. In vivo, Notch function appears to be critical for the proper differentiation of T and B lymphocytes, and γ-secretase inhibitors reduce the thymocyte number and block thymocyte differentiation at an early stage in fetal thymic organ cultures. 
         [0111]    The FBXW7 gene (also called hCDC4) encodes a key component of the E3 ubiquitin ligase that is implicated in the control of chromosome stability (Mao J. et. al, Nature 432, 775-779 (2004)). FBXW7 is responsible for binding the PEST domain of intracellular NOTCH1, leading to ubiquitination and degradation by the proteasome. Because there exists a statistically significant anti-correlation between PEST domain mutations in NOTCH1 and FBXW7 mutation in human T-ALL, T-ALL cells having a reduced expression/activity of FBXW7 will less likely to respond to γ-secretase inhibitors. 
         [0112]    One of the recurring problems of cancer therapy is that a patient in remission (after the initial treatment by surgery, chemotherapy, radiotherapy, or combination thereof) may experience relapse. The recurring cancer in those patients is frequently resistant to the apparently successful initial treatment. In fact, certain cancers in patients initially diagnosed with the disease may be already resistant to conventional cancer therapy even without first being exposed to such treatment. γ-secretase inhibitor therapy can be physically exhausting for the patient. Side effects of secretase inhibitors include weight loss, changes in gastrointestinal tract architecture, accumulation of necrotic cell debris, dilation of crypts and infiltration of inflammatory cells, nausea, vomiting, weakness, diarrhea elevation in white blood cell count, and esophageal failure (Siemers E. et al, 2005 May-June; 28(3):126-32; Wong, G T. et al, J Biol Chem. 2004 Mar. 26; 279 (13):12876-82). Thus there is a need to determine whether a cancer patient may benefit from a chemotherapeutic treatment prior to the commencement of the treatment. 
         [0113]    In one embodiment, a cancer patient is screened based on the expression level of FBXW7 and optionally, NOTCH1, in a cancer cell sample. 
         [0114]    The expression level of FBXW7 or NOTCH1 may be measured by DNA level, mRNA level, protein level, activity level, or other quantity reflected in or derivable from the gene or protein expression data. For example, a genetic alteration may result in a decreased expression of FBXW7. Common genetic alterations include deletion of at lease one FBXW7 gene from the genome, or a mutation in at least one allele of an FBXW7 gene. The mutation may be a mis-sense mutation; a non-sense mutation; an insertion, deletion, or substitution of one or more nucleotides; a truncation from the 5′ terminal (either untranslated region or coding region), 3′ terminal (either untranslated region or coding region), or both; a substitution of one or more nucleotides in the 5′ untranslated region, 3′ untranslated region, coding region (which results in an amino acid change), or combinations of the three. Exemplary genetic alterations include a mutation in the third WD40 domain or the fourth WD40 domain of the FBXW7, G423V, R465C, R465H, R479L. R479Q, R505C and D527G mutations. A genetic alteration may also result in an increased expression of NOTCH1, such as translocation or copy number amplification of NOTCH1 gene. 
         [0115]    The mRNA level of FBXW7 or NOTCH 1 may be measured using any art-known method, such as PCR, northern blotting, RNase Protection Assay, or microarray hybridization. For example, Real-time polymerase chain reaction, also called quantitative real time PCR (QRT-PCR) or kinetic polymerase chain reaction, is widely used in the art to measure mRNA level of a target gene. The QRT-PCR procedure follows the general pattern of polymerase chain reaction, but the DNA is quantified after each round of amplification. Two common methods of quantification are the use of fluorescent dyes that intercalate with double-strand DNA, and modified DNA oligonucleotide probes that fluoresce when hybridized with a complementary DNA. QRT-PCR can be combined with reverse transcription polymerase chain reaction to quantify low abundance messenger RNA (mRNA), enabling one to quantify relative gene expression at a particular time, or in a particular cell or tissue type. 
         [0116]    The expression level of FBXW7 or NOTCH1 may also be measured by protein level using any art-known method. Traditional methodologies for protein quantification include 2-D gel electrophoresis, mass spectrometry and antibody binding. Frequently used methods for assaying target protein levels in a biological sample include antibody-based techniques, such as immunoblotting (western blotting), immunohistological assay, enzyme linked immunosorbent assay (ELISA), radioimmunoassay (RIA), or protein chips. Gel electrophoresis, immunoprecipitation and mass spectrometry may be carried out using standard techniques. Additionally, NOTCH1 expression may be measured by detection of cleaved, intranuclear (ICN) form of NOTCH1 protein in cells. 
         [0117]    The expression level of FBXW7 or NOTCH1 may also be measured by the activity level of the gene product using any art-known method, such as transcriptional activity of NOTCH1 or ligase activity of FBXW7. For example, NOTCH1 activity may be measured by a increased binding of ICN of NOTCH1. Alternatively, the expression level of a transcriptional downstream target of NOTCH1 may be measured as an indicator of NOTCH1 activity, such as c-Myc, PTCRA, Hes1, etc. 
         [0118]    In certain embodiments, it is useful to compare the expression/activity level of FBXW7 or NOTCH1 to a control. The control may be a measure of the expression level of FBXW7 or NOTCH1 in a quantitative form (e.g., a number, ratio, percentage, graph, etc.) or a qualitative form (e.g., band intensity on a gel or blot, etc.). A variety of controls may be used. Levels of FBXW7 or NOTCH1 expression from a non-cancer cell of the same cell type from the subject may be used as a control. Levels of FBXW7 or NOTCH1 expression from the same cell type from a healthy individual may also be used as a control. Alternatively, the control may be expression levels of FBXW7 or NOTCH1 from the individual being treated at a time prior to treatment or at a time period earlier during the course of treatment. Still other controls may include expression levels present in a database (e.g., a table, electronic database, spreadsheet, etc.) or a pre-determined threshold. 
         [0119]    The present invention further discloses methods of treating a T-ALL subject who will likely be sensitive a treatment with γ-secretase inhibitors (identified using the methods described above), comprising administering to the patients a γ-secretase inhibitor. γ-secretase inhibitors are known in the art, exemplary γ-secretase inhibitors include LY450139 Dihydrate and LY411575. 
         [0120]    The present invention further discloses methods of treating a T-ALL subject who will has a decreased expression/activity of FBXW7 (identified using the methods described above) with an agent that increases the expression/activity of FBXW7. The agent may be a recombinant FBXW7 protein or a functionally active fragment or derivative thereof, a nuclei acid that encodes FBXW7 protein or a functionally active fragment or derivative thereof, or an agent that activates FBXW7. A “functionally active” PBXW7 fragment or derivative exhibits one or more functional activities associated with a full-length, wild-type FBXW7 protein, such as antigenic or immunogenic activity, ability to bind natural cellular substrates, etc. The functional activity of FBXW7 proteins, derivatives and fragments can be assayed by various methods known to one skilled in the art (Current Protocols in Protein Science, Coligan et al., eds., John Wiley &amp; Sons, Inc., Somerset, N.J. (1998)). 
         [0121]    In another aspect, the present invention provides a method for identifying subject with T-ALL who may benefit from treatment with a phosphatidylinositol 3-kinase (PI3K) pathway inhibitor, based on the discovery that PTEN inactivation is associated with human T-cell malignancy. 
         [0122]    PTEN has been characterized as a tumor suppressor gene that regulates cell cycle. PTEN functions as a phosphodiesterase and an inhibitor of the PI3K/AKT pathway, by removing the 3′ phosphate group of phosphatidylinositol (3,4,5)-trisphosphate (PIP 3 ). When PTEN is inactivated, increased production of PIP 3  activates AKT (protein kinase B). The AKT pathway promotes tumor progression by enhancing cell proliferation, growth, survival, and motility, and by suppressing apoptosis. AKT is activated by two phosphorylation events catalyzed by the phosphoinositide dependent kinase PDK1, an enzyme that is activated by PI3K. 
         [0123]    In one embodiment, the method for identifying subject with T-ALL who may benefit from treatment with a PI3K pathway inhibitor comprises: detecting in a tumor cell from the subject the expression level or activity level of PTEN. A decreased expression/activity of FBXW7, as compared to a control, indicates that the subject may benefit from a PI3K inhibitor therapy. 
         [0124]    The phospho-AKT level in the cancer cell from the subject may also be determined simultaneously; an increased phospho-AKT level, as compared to a control, further indicates that the subject may benefit from a PI3K inhibitor therapy. 
         [0125]    The expression level of PTEN may be measured by DNA level, mRNA level, protein level, activity level, or other quantity reflected in or derivable from the gene or protein expression data. For example, a genetic alteration may result in a decreased expression of PTEN. Common genetic alterations include deletion of at least one PTEN gene from the genome, or a mutation in at least one allele of a PTEN gene. The mutation may be a mis-sense mutation; a non-sense mutation; an insertion, deletion, or substitution of one or more nucleotides; a truncation from the 5′ terminal (either untranslated region or coding region), 3′ terminal (either untranslated region or coding region), or both; a substitution of one or more nucleotides in the 5′ untranslated region, 3′ untranslated region, coding region (which results in an amino acid change), or combinations of the three. 
         [0126]    The expression level of PTEN may also be measured by mRNA level using any method known in the art, such as PCR, Northern blotting, RNase Protection Assay, and microarray hybridization. 
         [0127]    The expression level of PTEN may also be measured by protein level using any method known in the art, such as 2-D gel electrophoresis, mass spectrometry and antibody binding 
         [0128]    The expression level of PTEN may also be measured by the activity level of PTEN using any art-known method, such as measuring the phosphatase activity. Additionally, the expression or activity of other proteins involved in the PI3K/AKT pathway may also be measured as a proxy for PTEN activity. For example, the phospho-AKT level in a cell generally reflects the PTEN activity, therefore may be measured as a marker for PTEN activity. 
         [0129]    In certain embodiments, a control may be used to compare the expression/activity level of PTEN. As described in detail above, a control may be derived from a non-cancer cell of the same type from the subject, same cell type from a healthy individual, a predetermined value, etc. 
         [0130]    The present invention further discloses methods of treating a T-ALL subject who may benefit from a treatment with PI3K inhibitors (identified using the methods described above), comprising administering to the patients a PI3K inhibitor. PI3K inhibitors are well know in the art (e.g., Pinna, L A and Cohen, P T W (eds.) Inhibitors of Protein Kinases and Protein Phosphates, Springer (2004) and Abelson, J N, Simon, M I, Hunter, T, Sefton, B M (eds.) Methods in Enzymology, Volume 201: Protein Phosphorylation, Part B: Analysis of Protein Phosphorylation, Protein Kinase Inhibitors, and Protein Academic Press (2007)). 
         [0131]    The present invention further discloses methods of treating a T-ALL subject who will has a decreased expression/activity of PTEN (identified using the methods described above) with an agent that increases the expression/activity of PTEN. The agent may be a recombinant PTEN protein or a functionally active fragment or derivative thereof, a nuclei acid that encodes PTEN protein or a functionally active fragment or derivative thereof, or an agent that activates PTEN. 
         [0132]    In another aspect, the invention provides a method of assessing whether a subject is afflicted with cancer or at risk for developing cancer, comprising: determining the expression or activity level of at least one cancer gene or candidate cancer gene located in an amplified MCR in Table 1 in a biological sample from the subject. An increase in the expression or activity the gene, as compared to a control, indicates that the subject is afflicted with cancer or at risk for developing cancer. Alternatively, if there is a decrease in the expression or activity of a cancer gene or candidate cancer gene located in a deleted MCR in Table 1, as compared to a control, the decreased expression or activity level also indicates that the subject is afflicted with cancer or at risk for developing cancer. 
         [0133]    In another aspect, the invention provides a method of assessing whether a subject is afflicted with cancer or at risk for developing cancer, the method comprising: determining the copy number of at least one amplified minimal common region (MCR) listed in Table 1 in a biological sample from the subject. An increased copy number of the MCR in the sample, as compared to the normal copy number of the MCR, indicates that the subject is afflicted with cancer or at risk for developing cancer. Alternatively, a decreased copy number of a deleted MCR (also listed in Table 1) in the sample, as compared to the normal copy number of the MCR, also indicates that the subject is afflicted with cancer or at risk for developing cancer. The normal copy number of an MCR is typically one per chromosome. 
         [0134]    In another aspect, the invention provides a method for monitoring the progression of cancer in a subject, the method comprising: a) determining in a biological sample from the subject at a first point in time, the expression or activity level of a cancer gene or a candidate cancer gene listed in Table 1; b) repeating step a) at a subsequent point in time; and c) comparing the expression or activity of the gene in steps a) and b), and therefrom monitoring the progression of cancer in the subject. 
         [0135]    In another aspect, the invention provides a method of assessing the efficacy of a test agent for treating a cancer in a subject, comprising: a) determining the expression or activity level of at least one cancer gene or a candidate cancer gene located in an amplified MCR in Table 1 in a biological sample from the subject in the presence of the test agent; and b) determining the expression or activity level of the gene in a biological sample from the subject in the absence of the test agent. A decreased expression or activity of the gene in step (a), as compared to that of (b), is indicative of the test agent&#39;s potential efficacy for treating the cancer in the subject. Alternatively, if the test agent increases the expression or activity of at least one cancer gene or a candidate cancer gene located in a deleted MCR in Table 1, the test agent is also potentially effective for treating the cancer in a subject. 
         [0136]    In another aspect, the invention provides a method of assessing the efficacy of a therapy for treating cancer in a subject, the method comprising: a) determining the expression or activity level of at least one cancer gene or a candidate cancer gene located in an amplified MCR in Table 1 in a biological sample from the subject prior to providing at least a portion of the therapy to the subject; and b) determining the expression or activity level of the gene in a biological sample from the subject following provision of the portion of the therapy. A decreased expression or activity of the gene in step (a), as compared to that of (b), is indicative of the therapy&#39;s efficacy for treating the cancer in the subject. Alternatively, if the therapy increases the expression or activity of at least one cancer gene or a candidate cancer gene located in a deleted MCR in Table 1, the therapy is also potentially effective for treating the cancer in a subject. 
         [0137]    In another aspect, the invention provides a method of treating a subject afflicted with cancer comprising administering to the subject an agent that decreases the expression or activity level of at least one cancer gene or candidate cancer gene located in am amplified MCR in Table 1. Alternatively, the invention provides a method of treating a subject afflicted with cancer comprising administering to the subject an agent that increases the expression or activity level of at least one cancer gene or candidate cancer gene located in a deleted MCR in Table 1. 
         [0138]    In certain embodiments, the agent is an antibody, or its antigen-binding fragment thereof, that specifically binds to a cancer gene or candidate cancer gene listed in Table 1. Optionally, the antibody may be conjugated to a toxin, or a chemotherapeutic agent. 
         [0139]    Alternatively, the agent may be an RNA interfering molecule (such as an shRNA or siRNA molecule) that inhibits expression of a cancer gene or candidate cancer gene in an amplified MCR in Table 1, or an antisense RNA molecule complementary to a cancer gene or candidate cancer gene in an amplified MCR in Table 1. 
         [0140]    Alternatively, the agent may be a peptide or peptidomimetic, a small organic molecule, or an aptamer. 
         [0141]    Preferrably, the agent is administered in a pharmaceutically acceptable formulation. 
         [0142]    In another aspect, the invention provides a method of assessing whether a subject is afflicted with cancer or at risk for developing cancer, the method comprising: determining the copy number of at least one minimal common region (MCR) listed in Table 5 in a biological sample from the subject. A change of copy number of the MCR in the sample, as compared to the normal copy number of the MCR, indicates that the subject is afflicted with cancer or at risk for developing cancer. The normal copy number of an MCR is typically one per chromosome. 
         [0143]    In certain embodiments, the cancer is lymphoma. In certain embodiments, the lymphoma is T-ALL. 
         [0144]    In another aspect, the invention provides a method of assessing whether a subject is afflicted with cancer or at risk for developing cancer, by comparing the copy number of an MCR, identified using a genome-unstable non-human mammal model (including a genome-unstable mouse model of the invention), with the normal copy number of the MCR. The normal copy number of an MCR is typically one per chromosome. 
       EXAMPLES 
     Example 1 
     Generation and Characterization of Murine T Cell Lymphomas with Highly Complex Genomes 
       [0145]    In this example, we created a murine lymphoma model system that combines the genome-destabilizing impact of Atm deficiency and telomere dysfunction to effect T lymphomagenesis in a p53-dependent manner. 
         [0146]    We interbred mTerc Atm p. 53 heterozygous mice and maintained them in pathogen-free conditions. We intercrossed the null alleles of mTerc, Atm and p53 to generate various genotypic combinations from this “triple”-mutant colony (for simplicity, hereafter designated as “TKO” for all genotypes from this colony). 
         [0147]    We monitored animals for signs of ill-health every other day. Moribund animals were euthanized and subjected to complete autopsy; mice found dead were subject to necropsy specifically for signs of lymphoma. We performed all animal uses and manipulations according to approved IACUC protocol. Tumors were harvested from TKO mice and partitioned in the following manner. One section was snap-frozen for DNA and RNA extraction, a second portion was processed for histology, and the remaining portion was disaggregated for in vitro culture. Suspensions of tumor cells were maintained in RPMI supplemented with 50 μM beta-mercaptoethanol, 10% Cosmic Calf serum (HyClone), 0.5 ng/ml recombinant IL-2, and 4 ng/ml recombinant IL-7 (both from Peprotech). Tumor cells were immunostained with antibodies against CD4, CD8, CD3, and B220/CD45R (eBioscience) and subjected to FACS analysis. 
         [0148]    We prepared DNA frozen tumors with the PureGene kit according to manufacturer&#39;s instructions (Gentra Systems). We prepared RNA by an initial extraction with Trizol (Invitrogen) according to the manufacturer&#39;s instructions. Pelleted total RNA was then digested with RQ1 DNase (Promega) and subsequently purified through RNA purification columns (Gentra). Proteins were obtained either from cell lines or tumor pieces by dis-aggregation in lysis buffer (according to Cell Signaling Technology) followed by sonication in a bath sonicator for 30 s. Lysates were clarified by centrifugation prior to quantification according to manufacturer&#39;s instructions (BioRad Protein Assay) and separation on 4-12% NuPage gels (Invitrogen). 
         [0149]    We found that TKO mice which are p53 +/−  or p53 −/−  succumbed to lethal lymphoma with shorter latency and higher penetrance relative to TKO animals wildtype for p53 ( FIG. 2A ). Moreover, lymphomas from TKO mice heterozygous for p53 showed reduction to homozygosity in 14 specimens (out of 15 specimens examined) ( FIG. 2B ), indicating strong genetic pressure to inactivate p53 during lymphomagenesis in this context. Phenotypically, these TKO tumors resembled lymphomas in the conventional Atm−/− mouse model with effacement of thymic architecture by CD4+/CD8+ (less commonly CD4−/CD8− or mixed single/double positive) lymphoma cells ( FIG. 2C ). Taken together, the genetic and molecular observations strongly suggest that an Atm-independent p53-dependent telomere checkpoint is operative to constrain lymphoma development. 
         [0150]    To quantify chromosomal rearrangements, we used Spectral Karyotype (SKY) analyses according to the following protocol. Metaphase preparations were typically obtained within 48 hours of establishment, although in a few instances establishment of the cell line was required to obtain good quality metaphases. Harvested cells were incubated in 105 mM KCl hypotonic buffer for 15 min prior to fixation in 3:1 methanol-acetic acid. Spectral karyotyping was done using the SkyPaint Kit and SkyView analytical software (Applied Spectral Imaging, Carlsbad, Calif.) according to manufacturer&#39;s protocols. Chromosome aberrations were defined using the rules from the Committee on Standard Genetic Nomenclature for Mice. T-test comparison between G0 and G1-G4 cytogenetics is based on 90 SKY profiles each set (ten metaphase spreads for each of TKO lymphomas). 
         [0151]      FIG. 1 ,  FIG. 2D , and Table 3 summarize the SKY analyses of chromosomal rearrangement in 9 telomere deficient (G1-G4 mTerc −/− ) TKO lymphomas and 9 telomere intact (G0 mTerc +/+  or mTerc +/− ) TKO lymphomas. Relative to G0 tumors, G1-G4 TKO lymphomas displayed an overall greater frequency of chromosome structural aberrations of various types (0.34 versus 0.09 per chromosome, respectively, p&lt;0.0001, t test) including a multitude of multi-centric chromosomes, non-reciprocal translocations (NRTs), p-p robertsonian-like translocations of homologous and/or non-homologous chromosomes, p-q fusions, and q-q fusions. When examined on a chromosome-by-chromosome basis, several chromosomes (specifically, 2, 6, 8, 14, 15, 16, 17, and 19) were involved in significantly more dicentric and robertsonian-like rearrangement events in G1-G4 relative to G0 TKO tumors (p&lt;0.05; t test;  FIG. 2E ). Without being bound by a particular theory, the recurrent non-random nature of these chromosomal rearrangements in the TKO model may provide adaptive mechanisms to tolerate telomere dysfunction and/or play causal roles in lymphoma development (e.g., chromosome 2, see below). 
       Example 2 
     TKO Lymphomas Harbor Genomic Alterations Syntenic to Those in Human T Cell Malignancy 
       [0152]    To assess the degree of syntenic overlap in the murine lymphoma-prone TKO instability model and in human T-ALL and other cancers, we applied and integrated multiple genome analysis technologies to survey cancer-associated alterations for comparison with T-ALL and a diverse set of major human cancers. 
         [0153]    Synteny describes the preserved order and orientation of genes between species. Disruption of synteny, caused by chromosome rearrangement, is an indication of divergent evolution. Comparisons of TKO mouse model and human T-ALL syntenic chromosomal regions may reveal the conserved nature of certain genetic modification in tumorigenesis. 
         [0154]    Because TKO lymphomas harbored a large number of complex nonreciprocal translocations (NRTs), we sought to determine whether these genome-unstable tumors possess increased numbers of recurrent amplifications and deletions. To this end, we compiled high-resolution genome-wide array-CGH profiles for 35 TKO tumors (Table 3) and 26 human T-ALL cell lines and tumors (Tables 4A and 4B) for comparison. 
         [0155]    T-ALL cell lines used in this example, and in Examples 3-7 are listed in Table 4A. A subset was subjected to both array-CGH (described in detail below) and re-sequencing, as indicated. 
         [0156]    We used two cohorts of clinical human T-ALL samples in this example. A cohort of 8 samples (Table 4B) comprised of cryopreserved lymphoblasts or lymphoblast cell lysates, obtained with informed consent and IRB approval at the time of diagnosis from pediatric patients with T-ALL treated on Dana-Farber Cancer Institute study 00-001. We subjected these samples to genome-wide array-CGH profiling. 
         [0157]    For genome-wide array-CGH profiling, we used the following protocol. Genomic DNA processing, labeling and hybridization to Agilent CGH arrays were performed as per manufacturer&#39;s protocol (http://www.home.agilent.com/agilent/home.jspx). Murine tumors were profiled against individual matched normal DNA (e.g., non-tumor cell of the same cell type from the same individual) or, when not available, pooled DNA of matching strain background. Labeled DNAs were hybridized onto 44K or 244K microarrays for mouse, and 22K or 44K microarrays for human. The Mouse 44K array contained 42,404 60-mer elements for which unique map positions were defined (National Center for Biotechnology Information, Mouse Build 34). The median interval between mapped elements was 21.8 kb, 97.1% of intervals of &lt;0.3 megabases (Mb), and 99.3% are &lt;1 Mb. The 244K array contained 224,641 elements for which unique map positions were defined based on the same mouse genome build. The Human 22K array contained 22,500 elements designed for expression profiling for which 16,097 unique map positions were defined with a median interval between mapped elements of 54.8 kb. The Human 44K microarray contained 42,494 60-mer oligonucleotide probes for which unique map positions were defined (National Center for Biotechnology Information, Human Build 35). The 244K array contained 226,932 60-mer oligonucleotide probes for which unique map positions were defined based on the same human genome build. 
         [0158]    Profiles generated on 244K density arrays were extracted for the same 42K probes on the 44K microarrays to allow combination of profiles generated on the two different platforms. Fluorescence ratios of scanned images were normalized and calculated as the average of two paired (dye swap), and copy number profile was generated based on Circular Binary Segmentation, an algorithm that uses permutation to determine the significance of change points in the raw data (A. B. Olshen, et al.,  Biostatistics  5 (4), 557 (2004)). 
         [0159]    TKO profiles revealed marked genome complexity with all chromosomes exhibiting recurrent CNAs—both regional and focal in nature ( FIG. 2F ). Many CNAs were highly recurrent, observed in more than 40% of samples (e.g., amplicons targeting distinct regions on mouse chromosomes 1, 2, 3, 4, 5, 9, 10, 12, 14, 15, 16, and 17; and deletions on 6, 11, 12, 13, 14, 16 and 19). These patterns of genomic alteration corresponded well with the SKY analyses showing predominant involvement of these chromosomes in rearrangement events. Attesting to the robustness and resolution of this platform, highly recurrent physiological deletions of the T cell receptor (Tcr) loci were readily detected ( FIG. 2F , arrows) as expected for clonal CD4/CD8-positive T-cells, e.g., chromosome 6 Tcrβ locus sustained focal deletion in 28/35 tumors, as well as focal deletions of chromosome 14 Tcrα/Tcrβ locus and chromosome 13 Tcrδ locus ( FIG. 1C ;  FIG. 2F ). 
         [0160]    The pathogenetic relevance of these recurrent genomic events, and of this instability model, is supported by integrated array-CGH and SKY analyses of a high amplitude genomic event on chromosome 2 in several independent TKO tumors. These CNAs shared a common boundary defined by array-CGH and contained a recurrent NRT involving the A3 band of chromosome 2 with different partner chromosomes by SKY ( FIG. 3 ). 
       Example 3 
     Frequent NOTCH1 Rearrangement in TKO Mouse Model 
       [0161]    For further comparison of genomic events in the TKO model and in human T-All, we used a separate series of 38 human clinical specimens (Table 4C) for re-sequencing of NOTCH 1, FBXW7 and PTEN (see Examples 5-6). These T-ALL samples were collected from 8 children and adolescents diagnosed at the Royal Free Hospital, London, and 30 adult patients enrolled in the MRC UKALL-XII trial. Appropriate informed consent was obtained from the patients (if over 18 years of age) or their guardians (if under 18 years), and the study had Ethics Committee approval. 
         [0162]    1. HPLC and Sequencing. Gene mutation status was established by denaturing high-performance liquid chromatography (see, e.g., M. R. Mansour, et al.,  Leukemia  20 (3), 537 (2006)), and by bidirectional sequencing. Briefly, genomic DNA was extracted using the Qiagen (Hilden, Germany) genomic purification kit. PCR primers were designed to amplify exons and flanking intronic sequences. PCR amplification and direct sequencing were done according to art-known methods (for details, see H. Davies, et al.,  Cancer Res  65 (17), 7591 (2005)). Sequence traces were analysed using a combination of manual analysis and software-based analyses, where deviation from normal is indicated by the presence of two overlapping sequencing traces (indicating the presence of one normal allelic and one mutant allelic DNA sequence), or the presence of a single sequence trace that deviates from normal (indicating the presence of only a mutant DNA allele). All variants were confirmed by bidirectional sequencing of a second independently amplified PCR product. 
         [0163]    2. Expression profiling. Biotinylated target cRNA was generated from total sample RNA from a TKO model and hybridized to mouse oligonucleotide probe arrays against normal control murine thymus RNA (Mouse Development Oligo Microarray, Agilent, Palo Alto, Calif.) according to manufacturer&#39;s protocols. Expression values for each gene were mapped to genomic positions based on National Center for Biotechnology Information Build 34 of the mouse genome. 
         [0164]    3. Real-Time PCR. To confirm genetic loci, Real-time PCR was performed with a Quantitect SYBR green kit (Qiagen USA, Valencia, Calif.) using 2 ng DNA from each tumor run in triplicate, on Applied Biosystems or Stratagene MX3000 realtime thermocyclers. Each triplicate run was performed twice; quantification was performed using the standard curve method and the average fold change for the combined run was calculated. Primer sequences are listed in Table 8. 
         [0165]    4. Western Blotting. Western blots were performed on clarified tumor lysates on PVDF membranes using the following antibodies: PTEN (9552), Akt (9272), phospho-Akt (9271), Notch1, activated Notch1 Val1744 (2421) (Cell Signaling Technology, Ipswich, Mass.), and tubulin (Sigma Chemical, St. Louis, Mo.), according to the manufacturer&#39;s instructions and developed with HRP-labeled secondary antibodies (Pierce; Rockford, Ill.) and enhanced chemiluminescent substrate. 
         [0166]    5. Common Boundary Analysis of NOTCH1. Detailed structural analysis of the common boundary of CNAs revealed Notch1 locus alterations with rearrangement close to the 3′ region of the Notch1 gene in four TKO tumors, and focal amplifications encompassing Notch1 in two additional tumors ( FIG. 3 ; data not shown). Notch1 activation by C-terminal structural alteration and point mutations is a signature event of human T-ALL (see, A. P. Weng, et al.,  Science  306 (5694), 269 (2004), F. Radtke, et al.,  Nat Immunol  5 (3), 247 (2004), L. W. Ellisen, et al.,  Cell  66 (4), 649 (1991)). Although the structure of the rearrangements in the TKO samples did not precisely mirror NOTCH1 translocations in human T-ALL (L. W. Ellisen, et al.,  Cell  66 (4), 649 (1991)), their common shared boundary involving Notch1 suggested potential relevance of the TKO tumors. Accordingly, we performed Notch1 re-sequencing in several TKO lymphomas without evidence of genomic rearrangement at this locus and uncovered truncating insertion/deletion mutations and non-conservative amino acid substitutions in the Notch1 PEST and heterodimerization (HD) domains, as well as one case of an intragenic 379 by deletion within exon 34 encoding the PEST domain (sample A1040) ( FIG. 4A ; Table 3). This mutation spectrum is similar to that observed in human T-ALL, as the PEST and HD domains are two hot spots of NOTCH1 mutation ( FIG. 4A , see below) (A. P. Weng, et al.,  Science  306 (5694), 269 (2004). Biochemically, various types of genomic rearrangements, intragenic deletions and mutations promoted activation of Notch1, as evidenced by Western blot assays designed to detect full-length protein and the active cleaved form (V1744) of Notch1 proteins ( FIG. 4B ) as well as by transcriptional profiles showing up-regulation of several Notch1 transcriptional targets including Ptcra, Hes1, Dtx1, and Cd3e that correlated well with mRNA levels of Notch1 (F. Radtke, et al.,  Nat Immunol  5 (3), 247 (2004)) ( FIG. 4C ). 
       Example 4 
     Determining Synteny Across Species by Ortholog Mapping of Genes within the Minimal Common Regions of Copy Number Alterations 
       [0167]    In this Example, We further assessed the CNAs in the TKO mouse model by defining and characterization the minimal common regions of CNAs. 
         [0168]    Synteny describes the preserved order and orientation of genes between species. Disruption of synteny, caused by chromosome rearrangement, is an indication of divergent evolution. Comparisons of TKO mouse model and human T-ALL syntenic chromosomal regions may reveal the conserved nature of certain genetic modification in tumorigenesis. 
         [0169]    The observation of physiological deletion of TCR loci and human-like pattern of Notch1 genomic and mutational events prompted us to assess the extent to which the highly unstable genome of the TKO model engendered CNAs targeting loci syntenic to CNAs in human T-ALL using ortholog mapping of genes resident within the minimal common regions (MCRs) of copy number alterations. 
         [0170]    1. Definition of MCRs. To facilitate this comparison, we first defined the MCRs in TKO genome by an established algorithm (see, e.g., D. R. Carrasco, et al.,  Cancer Cell  9 (4), 313 (2006); A. J. Aguirre, et al.,  Proc Natl Acad Sci USA  101 (24), 9067 (2004)) with criteria of CNA width&lt;=10 Mb and amplitude&gt;0.75 (log 2 scale). Briefly, a “segmented” dataset was generated by determining uniform copy number segment boundaries according to the method of Olshen (A. B. Olshen, et al.,  Biostatistics  5 (4), 557 (2004) and then replacing raw log 2 ratio for each probe by the mean log 2 ratio of the segment containing the probe. For 22K and 44K profiles, thresholds representing minimal CNA were chosen at ±0.15 and ±0.3, respectively. 
         [0171]    Thresholds representing CNAs were chosen at ±0.4 and ±0.6, respectively. Higher thresholds were used for 44K profiles comparing to 22K profiles to adjust for signal-to-noise detection difference in platform performance. For examples 3-6, w selected minimal common region (MCR) by requiring at least one sample to show an extreme CNA event, defined by a log 2 ratio of ±0.60 and ±0.75 for 22K and 44K profiles, respectively, and the width of MCR is less than 10 Mb. 
         [0172]    2. Homolog Mapping. We identified human homologs of genes identifies in regions of chromosomal structural alteration of CNAs within mouse TKO MCRs using NCBI HOMOLOGENE database. In parallel, we identified CNAs in seven human tumor datasets (pancreatic, glioblastoma, melanoma, lung, colorectal and multiple myeloma). The human homolog gene list was then used to merge with genes within CNAs of each of the seven human tumor datasets. 
         [0173]    3. Cancer Gene Mapping. For cancer gene mapping, the mouse homologs were obtained based on Sanger&#39;s Cancer Gene Census 55  (http://www.sanger.ac.uk/genetics/CGP/Census). The mouse cancer genes were then mapped to TKO&#39;s MCRs. 
         [0174]    We obtained a list of 160 MCRs with average sizes of 2.12 Mb (0.15-9.82 Mb) and 2.33 Mb (0.77-9.6 Mb) for amplifications and deletions, respectively (Table 5). This frequency of genomic alterations is comparable to that of most human cancer genomes (e.g.  FIG. 9A ) and significantly above the typical 20 to 40 events detected in most genetically engineered ‘genome-stable’ murine tumor models (e.g., R. C. O&#39;Hagan, et al.,  Cancer Res  63 (17), 5352 (2003); N. Bardeesy, et al.,  Proc Natl Acad Sci USA  103 (15), 5947 (2006); M. Kim, et al.,  Cell  125 (7), 1269 (2006); L. Zender, et al.,  Cell  125 (7), 1253 (2006)). When compared to similarly defined MCR list in human T-ALL, 18 of the 160 MCRs (11%) overlapped with defined genomic events present in the human counterpart (Table 1). 
         [0175]    In Table 1, each murine TKO MCR with syntenic overlap with an MCR in the human T-ALL dataset is listed, separated by amplification and deletion, along with its chromosomal location (Cytoband/Chr) and base number (Start and End, in Mb). The minimal size of each MCR is indicated in bp. Peak ratio refers to the maximal log 2 array-CGH ratio for each MCR. Rec refers to the number of tumors in which the MCR was defined. Cancer genes and candidate cancer genes located in the amplified MCRs and deleted MCRs are also listed. The NCBI accession numbers and identification numbers for these cancer genes and candidate cancer genes are listed in Table 9. 
         [0176]    To calculate the statistic significance of MCR overlap between mouse TKO and each of the human cancers of different histological types, we implemented a permutation test to determine the expected frequency of achieving the same degree of overlap between two genomes by chance alone. Specifically, we randomly generated simulated mouse genome containing the same number and sizes of amplification MCRs in the corresponding chromosomes as the actual TKO genome a similar set was created for each of the human cancer genomes. The number of overlapping amplifications between mouse and each human genome was calculated and stored. This simulation process was repeated 10,000 times. The p value for significance of amplification overlap was then calculated by dividing the frequency of randomly achieving the same or greater degree of overlap as actually observed during the 10,000 permutations by 10,000. p values for deletion overlap were calculated in a similar fashion. 
         [0177]    We concluded that this degree of overlap was not by chance. First, statistic significance (p=0.001 and 0.004 for deletions and amplifications, respectively) supports this conclusion, as demonstrated by the rigorous permutation testing to validate the significance of the cross-species overlap. Second, we identified several genes already known or implicated in T-ALL biology, such as Crebbp, Ikaros, and Abl, present within these identified syntenic MCRs. Together, these data support the relevance of this engineered murine model to a related uman cancer and its usefulness. 
       Example 5 
     Frequent Fbxw7 Inactivation in T-ALL 
       [0178]    In this example, We identified Fbxw7 gene as a target of frequent inactivation or deletion in the TKO mouse model. 
         [0179]    We observed that a few TKO tumors with minimal Notch1 expression exhibited elevated Notch4 or Jagged1 (Notch ligand) mRNA levels (data not shown). To investigate this observation, we conducted a more detailed examination of the genomic and expression status of known components in the Notch pathway The four core elements of the Notch signaling system include the Notch receptor, DSL (Delta, Serrate, Lag-2) ligands, CSL (CBF1, Suppressor of hairless, Lag-1) transcriptional cofactors, and target genes. Upon binding ligand the Notch signaling converts CSL from a transcriptional repressor to a transcriptional activator. TKO sample A577 was one of the two tumors harboring a syntenic MCR encompassing the Fbxw7 gene (MCR #18, Table 1). In human T-ALL, focal FBXW7 deletions including one case with a single-probe event were detected ( FIG. 5A , right panel). Although extremely focal, the syntenic overlap across species made it unlikely that such deletion events represented copy number polymorphism. Indeed, FBXW7 re-sequencing in a cohort of human T-ALL clinical specimens (n=38) and cell lines (n=23) (Tables 4A, 4C, 6) revealed that FBXW7 was mutated or deleted in 11/23 of the human cell lines (48%) and 11/38 of the clinical samples (29%), marking this gene as one of those most commonly mutated in human T-ALL (Table 2). Consistent with reduced expression of Fbxw7 relative to non-neoplastic thymus in 19 of the 24 TKO lymphomas ( FIG. 5B ), these FBXW7 mutations in human T-ALL were predominantly mis-sense mutations, and particularly clustered in evolutionarily conserved residues of the third and fourth WD40 domains of the protein ( FIG. 5C ). Furthermore, re-sequencing of FBXW7 in matched normal bone marrows from several patients in complete remission showed that the two most frequently mutated positions (R465, R479) were acquired somatically (data not shown); along the same line, none of the identified mutations were found in public SNP databases, attesting to the likelihood that these mutations were somatic in nature. Finally, 19 of the 21 mutations were heterozygous, consistent with previous reports that Fbxw7 may act as a haplo-insufficient tumour suppressor gene. 
         [0180]    FBXW7 is a key component of the E3 ubiquitin ligase responsible for binding the PEST domain of intracellular NOTCH1, leading to ubiquitination and degradation by the proteasome (N. Gupta-Rossi, et al.,  J Biol Chem  276 (37), 34371 (2001); C. Oberg, et al.,  J Biol Chem  276 (38), 35847 (2001); G. Wu, et al.,  Mol Cell Biol  21 (21), 7403 (2001)). PEST domain mutations in human T-ALL are thought to prolong the half-life of intracellular NOTCH1, raising the possibility that loss of FBXW7 function may cause similar effects on this pathway. To address this, we additionally characterized the human cell lines and clinical samples for NOTCH1 mutations (Table 2; Tables 4A, 4C, 6). Interestingly, there was no association between known functional mutations of NOTCH1 (HD-N, HD-C and PEST domains) and FBXW7 mutations (p=0.16). However, among samples with NOTCH1 mutations, FBXW7 mutations were found less frequently in samples with a mutated PEST domain (4/19; 21%) than samples with mutations of only the HD-N or HD-C domain (13/20; 65%; p=0.009 by Fisher exact test). One explanation of this observation is that mutations of FBXW7 and the PEST domain of NOTCH1 target the same degradation pathway, and little selective advantage accrues to the majority of leukaemias from mutating both components. At the same time, the lack of NOTCH1 and FBXW7 mutual exclusivity may suggest non-overlapping activities by FBXW7 on pathways other than NOTCH signaling. 
       Example 6 
     Pten Inactivation is a Common Event in Mouse and Human T-Cell Malignancy 
       [0181]    In this example, We identified Pten gene as a target of frequent inactivation or deletion in the TKO mouse model. 
         [0182]    Focal deletion on chromosome 19, centering on the Pten gene, was among the most common genomic event in TKO lymphomas (Table 1,  FIG. 2F ). Using array-CGH, coupled with real-time PCR verification, we documented homozygous deletions of Pten in 15/35 (43%) TKO lymphomas ( FIG. 6 ,  FIG. 7A ). PTEN is a well-known tumor suppressor and its inactivation in the murine thymus is known to generate T cell tumors (A. Suzuki, et al.,  Curr Biol  8 (21), 1169 (1998)). Correspondingly, array-CGH confirmed that 4 of the 26 human T-ALL samples (2 cell lines and 2 primary tumors) had sustained PTEN locus rearrangements. Additionally, re-sequencing of the 61 T-ALL cell lines and clinical specimens (Table 4) uncovered inactivating PTEN mutations in 9 cases (none of which were found in public SNP databases), but with no clear correlation with status of NOTCH1 mutations (Table 2, Table 6). In addition, we observed that PTEN mutations occurred more frequently in cell lines (7/23; 30.4%) than in clinical specimens (2/38; 5.2%) (Table 6). As these clinical specimens were derived from newly diagnosed cases whilst the cell lines were established primarily from relapses, without being bound by a particular theory, this difference in mutation frequency may suggest that PTEN inactivation is a later event associated with progression, among other possibilities. 
         [0183]    In addition to these genomic and genetic alterations, Northern and Western blot analyses and transcriptome profiling of the TKO and human T-ALL samples revealed a broader collection of tumors with low to undetectable PTEN expression ( FIG. 7B , data not shown) with elevated phosphor-AKT. In addition to low PTEN expression, there appears to be additional mechanisms driving AKT activation as evidenced by the presence of focal Akt1 amplification and Tsc1 loss in two TKO samples ( FIG. 7C ; data not shown). Lastly, the biological significance of Pten status in TKO lymphoma is supported by their sensitivity to Akt inhibition in a Pten dependent manner ( FIG. 8 ) in response to triciribine, a drug known to block Akt phosphorylation and shown to inhibit cells dependent on the Akt pathway. Briefly, twenty thousand cells were plated in triplicate in 96-well format and were incubated in standard media with varying doses of triciribine (BioMol, Plymouth Meeting, Pa.) or an equivalent concentration of vehicle (DMSO; Sigma Chemical, St. Louis, Mo.) for 2 days at 37° C., 5% CO2. At the end of the incubation period, cell growth was quantified with MTS assay (AqueousOne Cell Titer System; Promega, Madison, Wis.) and absorbance read at OD490. Relative cell growth was plotted against growth of the cell line in the equivalent amount DMSO alone. Experiments were repeated 3-5 times for each cell line and dose. As shown in  FIG. 8 , TKO cells with Pten mutations or deletions were sensitive to tricibine. 
       Example 7 
     Broad Comparison of TKO Genome with Diverse Human Cancers 
       [0184]    In examples 3-6, Applicant identified and characterized Fbxw7 and Pten using the TKO mouse model. Both Fbxw7 and Pten have been previously identified as tumor suppressor genes. Thus their identification as mutated in human T-ALL provided proof of principle for the Applicants&#39; approach and demonstrated that the mouse model described herein provides a powerful tool to cancer gene discovery. In this example, Applicants extended the cross-species genomic analyses to other human cancers. 
         [0185]    While above cross-species comparison showed numerous concordant lesions in cancers of T cell origin, the fact that this instability model is driven by mechanisms of fundamental relevance (e.g., telomere dysfunction and p53 mutation) to many cancer types, including non-hematopoietic malignancies, suggested potentially broader relevance to other human cancers. A case in point is the Pten example above, in that PTEN is a bona fide tumor suppressor for multiple cancer types 49,50 . To assess this, we extended the cross-species comparative genomic analyses to 6 other human cancer types (n=421) of hematopoietic, mesenchymal and epithelial origins, including multiple myeloma (n=67) 53 , glioblastoma (n=38) (unpublished) and melanoma (n=123) (unpublished), as well as adenocarcinomas of the pancreas (n=30) (unpublished), lung (n=63) 54  and colon (n=74) (unpublished). 
         [0186]    Compared against similarly defined MCR lists (i.e. MCR width&lt;=10 Mb; see Example 4 and  FIG. 5A ) of each of these cancer types, Applicants found that 102 (61 amplifications and 41 deletions) of the 160 MCRs (64%) in the TKO genomes matched with at least one MCR in one human array-CGH dataset ( FIG. 5A ), with strong statistical significance attesting to non-randomness of this degree of overlap. Confidence in the genetic relevance of these syntenic events was further bolstered by the observation that more than half of these syntenic MCRs (38 of 61 amplifications or 62%; 22 of 41 deletions or 53%) overlapped with MCRs recurrent in two or more human tumor types ( FIG. 5B ). Moreover, a significant proportion of the TKO MCRs are evolutionarily conserved in human tumors of non-hematopoietic origin ( FIG. 5C ). Among the 61 amplifications with syntenic hits, 58 of them (95%) were observed in solid tumors, while the remaining 3 were uniquely found in myeloma ( FIG. 5C ). Similarly, 33 of the 41 (80%) syntenic deletions were present in solid tumors ( FIG. 5C ). In particular, Applicants found that p53 was present in a deletion MCR in 5 of 7 human cancer types, while Myc was the target of an amplification that overlapped with 6 human cancers. This substantial overlap with diverse human cancers was unexpected. 
         [0187]    Next, Applicants determined whether these syntenic MCRs targeted known cancer genes to provide an additional level of validation for these TKO genomic events. Among the 363 genes listed on the Cancer Gene Census 55 , 237 genes have a mouse homolog based on NCBI homologene (see Example 4). Of these, 24 known cancer genes were found to be resident within one of the 104 syntenic MCRs (Table 7). These included 17 oncogenes in amplifications and 7 tumor suppressor genes in deletions. The majority of these syntenic MCRs do not contain known cancer genes, raising the strong possibility that re-sequencing focused on resident genes of syntenic MCRs may provide a high-yield strategy to identify somatic mutations in human cancers, a thesis supported by the FBXW7 and PTEN examples. 
         [0188]    The practice of the various aspects of the present invention may employ, unless otherwise indicated, conventional techniques of cell biology, cell culture, molecular biology, transgenic biology, microbiology, recombinant DNA, and immunology, which are within the skill of the art. Such techniques are explained fully in the literature. See, for example,  Molecular Cloning A Laboratory Manual,  2nd Ed., ed. by Sambrook, Fritsch and Maniatis (Cold Spring Harbor Laboratory Press: 1989);  DNA Cloning , Volumes I and II (D. N. Glover ed., 1985);  Current Protocols in Molecular Biology , by Ausubel et al., Greene Publishing Associates (1992, and Supplements to 2003);  Oligonucleotide Synthesis  (M. J. Gait ed., 1984); Mullis et al. U.S. Pat. No. 4,683,195;  Nucleic Acid Hybridization  (B. D. Hames &amp; S. J. Higgins eds. 1984);  Transcription And Translation  (B. D. Hames &amp; S. J. Higgins eds. 1984);  Culture Of Animal Cells  (R. I. Freshney, Alan R. Liss, Inc., 1987);  Immobilized Cells And Enzymes  (IRL Press, 1986); B. Perbal,  A Practical Guide To Molecular Cloning  (1984); the treatise,  Methods In Enzymology  (Academic Press, Inc., N.Y.);  Gene Transfer Vectors For Mammalian Cells  (J. H. Miller and M. P. Calos eds., 1987, Cold Spring Harbor Laboratory);  Methods In Enzymology , Vols. 154 and 155 (Wu et al. eds.),  Immunochemical Methods In Cell And Molecular Biology  (Mayer and Walker, eds., Academic Press, London, 1987);  Handbook Of Experimental Immunology , Volumes I-IV (D. M. Weir and C. C. Blackwell, eds., 1986);  Manipulating the Mouse Embryo , (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1986); Coffin et al.,  Retroviruses , Cold Spring Harbor Laboratory Press; Cold Spring Harbor, N.Y. (1997); Bast et al.,  Cancer Medicine,  5th ed., Frei, Emil, editors, BC Decker Inc., Hamilton, Canada (2000); Lodish et al.,  Molecular Cell Biology,  4th ed., W. H. Freeman &amp; Co., New York (2000); Griffiths et al.,  Introduction to Genetic Analysis,  7th ed., W. H. Freeman &amp; Co., New York (1999); Gilbert et al.,  Developmental Biology,  6th ed., Sinauer Associates, Inc., Sunderland, Mass. (2000); and Cooper,  The Cell—A Molecular Approach,  2nd ed., Sinauer Associates, Inc., Sunderland, Mass. (2000). All patents, patent applications and references cited herein are incorporated in their entirety by reference. 
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       SEQUENCES 
       [0213]    Mm Dvl1 cDNA ( Homo sapiens ) 
         [0000]                                      SEQ ID NO: 1                1   atggcggaga ccaagattat ctaccacatg gacgaggagg agacgccgta               cctggtcaag               61   ctgcccgtgg cccccgagcg cgtcacgctg gccgacttca agaacgtgct           cagcaaccgg               121   cccgtgcacg cctacaaatt cttctttaag tccatggacc aggacttcgg           ggtggtgaag               181   gaggagatct ttgatgacaa tgccaagctt ccctgcttca acggccgcgt           ggtctcctgg               241   ctggtcctgg ctgagggtgc tcactcggat gcggggtccc agggcacgga           cagccacaca               301   gacctgcccc cgcctcttga gcggacaggc ggcatcgggg actcccggcc           cccctccttc               361   cacccaaatg tggccagcag ccgtgacggg atggacaacg agacaggcac           ggagtccatg               421   gtcagtcacc ggcgggagcg tgcccgacgc cggaaccgcg aggaggccgc           ccggaccaat               481   gggcacccaa ggggagaccg acggcgggat gtggggctgc ccccagacag           cgcgtccacc               541   gccctcagca gcgagcttga gtccagcagc tttgtggact cggacgagga           tggcagcacg               601   agcaggctca gcagctccac ggagcagagc acctcatcca gactcatccg           gaagcacaaa               661   cgccggcgga ggaagcagcg ccttcggcag gcggaccggg cctcctcctt           cagcagcata               721   accgactcca ccatgtccct caacatcgtc actgtcacgc tcaacatgga           aagacatcac               781   tttctgggca tcagcatcgt ggggcagagc aacgaccgtg gagacggcgg           catctacatt               841   ggctccatca tgaagggcgg ggctgtggcc gctgacggcc gcatcgagcc           cggcgacatg               901   ttgctgcagg tgaatgacgt gaactttgag aacatgagca atgacgatgc           cgtgcgggtg               961   ctgcgggaga tcgtttccca gacggggccc atcagcctca ctgtggccaa           gtgctgggac               1021   ccaacgcccc gaagctactt caccgtccca cgggctgacc cggtgcggcc           catcgacccc               1081   gccgcctggc tgtcccacac ggcggcactg acaggagccc tgccccgcta           cgagctggaa               1141   gaggcgccgc tgacggtgaa gagtgacatg agcgccgtcg tccgggtcat           gcagctgcca               1201   gactcgggac tggagatccg cgaccgcatg tggctcaaga tcaccatcgc           caatgccgtc               1261   atcggggcgg acgtggtgga ctggctgtac acacacgtgg agggcttcaa           ggagcggcgg               1321   gaggcccgga agtacgccag cagcttgctg aagcacggct tcctgcggca           cacggtcaac               1381   aagatcacct tctccgagca gtgctactac gtcttcgggg atctctgcag           caatctcgcc               1441   accctgaacc tcaacagtgg ctccagtggg acttcggatc aggacacgct           ggccccgctg               1501   ccccacccgg ctgccccctg gcctctgggt cagggctacc cctaccagta           cccgggaccc               1561   ccaccctgct tcccgcctgc ctaccaggac ccgggcttta gctatggcag           cggcagcacc               1621   gggagtcagc agagtgaagg gagcaaaagc agtgggtcca cccggagcag           ccgccgggcc               1681   ccgggccgtg agaaggagcg tcgggcggcg ggagctgggg gcagtggcag           tgaatcggat               1741   cacacggcac cgagtggggt ggggagcagc tggcgagagc gtccggccgg           ccagctcagc               1801   cgtggcagca gcccacgcag tcaggcctcg gctaccgccc cggggctccc           cccgccccac               1861   cccacgacca aggcctatac agtggtgggg gggccacccg ggggaccccc           tgtccgggag               1921   ctggctgccg tccccccgga attgacaggc agccgccagt ccttccagaa           ggctatgggg               1981   aacccctgcg agttcttcgt ggacatcatg tga            
Mm DVL1 protein ( Homo sapiens )
 
         [0000]                              SEQ ID NO: 2            1   maetkiiyhm deeetpylvk lpvapervtl adfknvlsnr           pvhaykfffk smdqdfgvvk               61   eeifddnakl pcfngrvvsw lvlaegahsd agsqgtdsht           dlppplertg gigdsrppsf               121   hpnvassrdg mdnetgtesm vshrrerarr rnreeaartn           ghprgdrrrd vglppdsast               181   alsselesss fvdsdedgst srlsssteqs tssrlirkhk           rrrrkqrlrq adrassfssi               241   tdstmslniv tvtlnmerhh flgisivgqs ndrgdggiyi           gsimkggava adgriepgdm               301   llqvndvnfe nmsnddavrv lreivsqtgp isltvakcwd           ptprsyftvp radpvrpidp               361   aawlshtaal tgalpryele eapltvksdm savvrvmqlp           dsgleirdrm wlkitianav               421   igadvvdwly thvegfkerr earkyassll khgflrhtvn           kitfseqcyy vfgdlcsnla               481   tlnlnsgssg tsdqdtlapl phpaapwplg qgypyqypgp           ppcfppayqd pgfsygsgst               541   gsqqsegsks sgstrssrra pgrekerraa gaggsgsesd           htapsgvgss wrerpagqls               601   rgssprsqas atapglppph pttkaytvvg gppggppvre           laavppeltg srqsfqkamg               661   npceffvdim            
Ccnl2 cDNA ( Homo sapiens )
 
         [0000]                                      SEQ ID NO: 3                1   atggcggcgg cggcggcggc ggctggtgct gcagggtcgg cagctcccgc               ggcagcggcc               61   ggcgccccgg gatctggggg cgcaccctca gggtcgcagg gggtgctgat           cggggacagg               121   ctgtactccg gggtgctcat caccttggag aactgcctcc tgcctgacga           caagctccgt               181   ttcacgccgt ccatgtcgag cggcctcgac accgacacag agaccgacct           ccgcgtggtg               241   ggctgcgagc tcatccaggc ggccggtatc ctgctccgcc tgccgcaggt           ggccatggct               301   accgggcagg tgttgttcca gcggttcttt tataccaagt ccttcgtgaa           gcactccatg               361   gagcatgtgt caatggcctg tgtccacctg gcttccaaga tagaagaggc           cccaagacgc               421   atacgggacg tcatcaatgt gtttcaccgc cttcgacagc tgagagacaa           aaagaagccc               481   gtgcctctac tactggatca agattatgtt aatttaaaga accaaattat           aaaggcggaa               541   agacgagttc tcaaagagtt gggtttctgc gtccatgtga agcatcctca           taagataatc               601   gttatgtacc ttcaggtgtt agagtgtgag cgtaaccaac acctggtcca           gacctcatgg               661   aattacatga acgacagcct tcgcaccgac gtcttcgtgc ggttccagcc           agagagcatc               721   gcctgtgcct gcatttatct tgctgcccgg acgctggaga tccctttgcc           caatcgtccc               781   cattggtttc ttttgtttgg agcaactgaa gaagaaattc aggaaatctg           cttaaagatc               841   ttgcagcttt atgctcggaa aaaggttgat ctcacacacc tggagggtga           agtggaaaaa               901   agaaagcacg ctatcgaaga ggcaaaggcc caagcccggg gcctgttgcc           tgggggcaca               961   caggtgctgg atggtacctc ggggttctct cctgccccca agctggtgga           atcccccaaa               1021   gaaggtaaag ggagcaagcc ttccccactg tctgtgaaga acaccaagag           gaggctggag               1081   ggcgccaaga aagccaaggc ggacagcccc gtgaacggct tgccaaaggg           gcgagagagt               1141   cggagtcgga gccggagccg tgagcagagc tactcgaggt ccccatcccg           atcagcgtct               1201   cctaagagga ggaaaagtga cagcggctcc acatctggtg ggtccaagtc           gcagagccgc               1261   tcccggagca ggagtgactc cccaccgaga caggcccccc gcagcgctcc           ctacaaaggc               1321   tctgagattc ggggctcccg gaagtccaag gactgcaagt acccccagaa           gccacacaag               1381   tctcggagcc ggagttcttc ccgttctcga agcaggtcac gggagcgggc           ggataatccg               1441   ggaaaataca agaagaaaag tcattactac agagatcagc gacgagagcg           ctcgaggtcg               1501   tatgaacgca caggccgtcg ctatgagcgg gaccaccctg ggcacagcag           gcatcggagg               1561   tga            
CCNL2 protein ( Homo sapiens )
 
         [0000]                              SEQ ID NO: 4            1   maaaaaaaga agsaapaaaa gapgsggaps gsqgvligdr           lysgvlitle ncllpddklr               61   ftpsmssgld tdtetdlrvv gceliqaagi llrlpqvama           tgqvlfqrff ytksfvkhsm               121   ehvsmacvhl askieeaprr irdvinvfhr lrqlrdkkkp           vpllldqdyv nlknqiikae               181   rrvlkelgfc vhvkhphkii vmylqvlece rnqhlvqtsw           nymndslrtd vfvrfqpesi               241   acaciylaar tleiplpnrp hwfllfgate eeiqeiclki           lqlyarkkvd lthlegevek               301   rkhaieeaka qargllpggt qvldgtsgfs papklvespk           egkgskpspl svkntkrrle               361   gakkakadsp vnglpkgres rsrsrsreqs ysrspsrsas           pkrrksdsgs tsggsksqsr               421   srsrsdsppr qaprsapykg seirgsrksk dckypqkphk           srsrsssrsr srsreradnp               481   gkykkkshyy rdqrrersrs yertgrryer dhpghsrhrr            
Aurkaip1 cDNA ( Homo sapiens )
 
         [0000]                              SEQ ID NO: 5            1   atgctcctgg ggcgcctgac ttcccagctg ttgagggccg           ttccttgggc aggcggccgc               61   ccgccttggc ccgtctctgg agtgctgggc agccgggtct           gcgggcccct ttacagcaca               121   tcgccggccg gcccaggtag ggcggcctct ctccctcgca           agggggccca gctggagctg               181   gaggagatgc tggtccccag gaagatgtcc gtcagccccc           tggagagctg gctcacggcc               241   cgctgcttcc tgcccagact ggataccggg accgcaggga           ctgtggctcc accgcaatcc               301   taccagtgtc cgcccagcca gataggggaa ggggccgagc           agggggatga aggcgtcgcg               361   gatgcgcctc aaattcagtg caaaaacgtg ctgaagatcc           gccggcggaa gatgaaccac               421   cacaagtacc ggaagctggt gaagaagacg cggttcctgc           ggaggaaggt ccaggaggga               481   cgcctgagac gcaagcagat caagttcgag aaagacctga           ggcgcatctg gctgaaggcg               541   gggctaaagg aagcccccga aggctggcag acccccaaga           tctacctgcg gggcaaatga            
AURKAIP1 Protein ( Homo sapiens )
 
         [0000]                              SEQ ID NO: 6            1   mllgrltsql lravpwaggr ppwpvsgvlg srvcgplyst           spagpgraas lprkgaqlel               61   eemlvprkms vspleswlta rcflprldtg tagtvappqs           yqcppsqige gaeqgdegva               121   dapqiqcknv lkirrrkmnh hkyrklvkkt rflrrkvqeg           rlrrkqikfe kdlrriwlka               181   glkeapegwq tpkiylrgk            
Myb cDNA ( Homo sapiens )
 
         [0000]                                      SEQ ID NO: 7                1   atggcccgaa gaccccggca cagcatatat agcagtgacg aggatgatga               ggactttgag               61   atgtgtgacc atgactatga tgggctgctt cccaagtctg gaaagcgtca           cttggggaaa               121   acaaggtgga cccgggaaga ggatgaaaaa ctgaagaagc tggtggaaca           gaatggaaca               181   gatgactgga aagttattgc caattatctc ccgaatcgaa cagatgtgca           gtgccagcac               241   cgatggcaga aagtactaaa ccctgagctc atcaagggtc cttggaccaa           agaagaagat               301   cagagagtga tagagcttgt acagaaatac ggtccgaaac gttggtctgt           tattgccaag               361   cacttaaagg ggagaattgg aaaacaatgt agggagaggt ggcataacca           cttgaatcca               421   gaagttaaga aaacctcctg gacagaagag gaagacagaa ttatttacca           ggcacacaag               481   agactgggga acagatgggc agaaatcgca aagctactgc ctggacgaac           tgataatgct               541   atcaagaacc actggaattc tacaatgcgt cggaaggtcg aacaggaagg           ttatctgcag               601   gagtcttcaa aagccagcca gccagcagtg gccacaagct tccagaagaa           cagtcatttg               661   atgggttttg ctcaggctcc gcctacagct caactccctg ccactggcca           gcccactgtt               721   aacaacgact attcctatta ccacatttct gaagcacaaa atgtctccag           tcatgttcca               781   taccctgtag cgttacatgt aaatatagtc aatgtccctc agccagctgc           cgcagccatt               841   cagagacact ataatgatga agaccctgag aaggaaaagc gaataaagga           attagaattg               901   ctcctaatgt caaccgagaa tgagctaaaa ggacagcagg tgctaccaac           acagaaccac               961   acatgcagct accccgggtg gcacagcacc accattgccg accacaccag           acctcatgga               1021   gacagtgcac ctgtttcctg tttgggagaa caccactcca ctccatctct           gccagcggat               1081   cctggctccc tacctgaaga aagcgcctcg ccagcaaggt gcatgatcgt           ccaccagggc               1141   accattctgg ataatgttaa gaacctctta gaatttgcag aaacactcca           atttatagat               1201   tctttcttaa acacttccag taaccatgaa aactcagact tggaaatgcc           ttctttaact               1261   tccacccccc tcattggtca caaattgact gttacaacac catttcatag           agaccagact               1321   gtgaaaactc aaaaggaaaa tactgttttt agaaccccag ctatcaaaag           gtcaatctta               1381   gaaagctctc caagaactcc tacaccattc aaacatgcac ttgcagctca           agaaattaaa               1441   tacggtcccc tgaagatgct acctcagaca ccctctcatc tagtagaaga           tctgcaggat               1501   gtgatcaaac aggaatctga tgaatctgga attgttgctg agtttcaaga           aaatggacca               1561   cccttactga agaaaatcaa acaagaggtg gaatctccaa ctgataaatc           aggaaacttc               1621   ttctgctcac accactggga aggggacagt ctgaataccc aactgttcac           gcagacctcg               1681   cctgtggcag atgcaccgaa tattcttaca agctccgttt taatggcacc           agcatcagaa               1741   gatgaagaca atgttctcaa agcatttaca gtacctaaaa acaggtccct           ggcgagcccc               1801   ttgcagcctt gtagcagtac ctgggaacct gcatcctgtg gaaagatgga           ggagcagatg               1861   acatcttcca gtcaagctcg taaatacgtg aatgcattct cagcccggac           gctggtcatg               1921   tga            
MYB Protein ( Homo sapiens )
 
         [0000]                              SEQ ID NO: 8            1   marrprhsiy ssdeddedfe mcdhdydgll pksgkrhlgk           trwtreedek lkklveqngt               61   ddwkvianyl pnrtdvqcqh rwqkvlnpel ikgpwtkeed           qrvielvqky gpkrwsviak               121   hlkgrigkqc rerwhnhlnp evkktswtee edriiyqahk           rlgnrwaeia kllpgrtdna               181   iknhwnstmr rkveqegylq esskasqpav atsfqknshl           mgfaqappta qlpatgqptv               241   nndysyyhis eaqnvsshvp ypvalhvniv nvpqpaaaai           qrhyndedpe kekrikelel               301   llmstenelk gqqvlptqnh tcsypgwhst tiadhtrphg           dsapvsclge hhstpslpad               361   pgslpeesas parcmivhqg tildnvknll efaetlqfid           sflntssnhe nsdlempslt               421   stplighklt vttpfhrdqt vktqkentvf rtpaikrsil           essprtptpf khalaaqeik               481   ygplkmlpqt pshlvedlqd vikqesdesg ivaefqengp           pllkkikqev esptdksgnf               541   fcshhwegds lntqlftqts pvadapnilt ssvlmapase           dednvlkaft vpknrslasp               601   lqpcsstwep ascgkmeeqm tsssqarkyv nafsartlvm            
Ahi1 cDNA ( Homo sapiens )
 
         [0000]                                      SEQ ID NO: 9                1   atgcctacag ctgagagtga agcaaaagta aaaaccaaag ttcgctttga               agaattgctt               61   aagacccaca gtgatctaat gcgtgaaaag aaaaaactga agaaaaaact           tgtcaggtct               121   gaagaaaaca tctcacctga cactattaga agcaatcttc actatatgaa           agaaactaca               181   agtgatgatc ccgacactat tagaagcaat cttccccata ttaaagaaac           tacaagtgat               241   gatgtaagtg ctgctaacac taacaacctg aagaagagca cgagagtcac           taaaaacaaa               301   ttgaggaaca cacagttagc aactgaaaat cctaatggtg atgctagtgt           agaggaagac               361   aaacaaggaa agccaaataa aaaggtgata aagacggtgc cccagttgac           tacacaagac               421   ctgaaaccgg aaactcctga gaataaggtt gattctacac accagaaaac           acatacaaag               481   ccacagccag gcgttgatca tcagaaaagt gagaaggcaa atgagggaag           agaagagact               541   gatttagaag aggatgaaga attgatgcaa gcatatcagt gccatgtaac           tgaagaaatg               601   gcaaaggaga ttaagaggaa aataagaaag aaactgaaag aacagttgac           ttactttccc               661   tcagatactt tattccatga tgacaaacta agcagtgaaa aaaggaaaaa           gaaaaaggaa               721   gttccagtct tctctaaagc tgaaacaagt acattgacca tctctggtga           cacagttgaa               781   ggtgaacaaa agaaagaatc ttcagttaga tcagtttctt cagattctca           tcaagatgat               841   gaaataagct caatggaaca aagcacagaa gacagcatgc aagatgatac           aaaacctaaa               901   ccaaaaaaaa caaaaaagaa gactaaagca gttgcagata ataatgaaga           tgttgatggt               961   gatggtgttc atgaaataac aagccgagat agcccggttt atcccaaatg           tttgcttgat               1021   gatgaccttg tcttgggagt ttacattcac cgaactgata gacttaagtc           agattttatg               1081   atttctcacc caatggtaaa aattcatgtg gttgatgagc atactggtca           atatgtcaag               1141   aaagatgata gtggacggcc tgtttcatct tactatgaaa aagagaatgt           ggattatatt               1201   cttcctatta tgacccagcc atatgatttt aaacagttaa aatcaagact           tccagagtgg               1261   gaagaacaaa ttgtatttaa tgaaaatttt ccctatttgc ttcgaggctc           tgatgagagt               1321   cctaaagtca tcctgttctt tgagattctt gatttcttaa gcgtggatga           aattaagaat               1381   aattctgagg ttcaaaacca agaatgtggc tttcggaaaa ttgcctgggc           atttcttaag               1441   cttctgggag ccaatggaaa tgcaaacatc aactcaaaac ttcgcttgca           gctatattac               1501   ccacctacta agcctcgatc cccattaagt gttgttgagg catttgaatg           gtggtcaaaa               1561   tgtccaagaa atcattaccc atcaacactg tacgtaactg taagaggact           gaaagttcca               1621   gactgtataa agccatctta ccgctctatg atggctcttc aggaggaaaa           aggtaaacca               1681   gtgcattgtg aacgtcacca tgagtcaagc tcagtagaca cagaacctgg           attagaagag               1741   tcaaaggaag taataaagtg gaaacgactc cctgggcagg cttgccgtat           cccaaacaaa               1801   cacctcttct cactaaatgc aggagaacga ggatgttttt gtcttgattt           ctcccacaat               1861   ggaagaatat tagcagcagc ttgtgccagc cgggatggat atccaattat           tttatatgaa               1921   attccttctg gacgtttcat gagagaattg tgtggccacc tcaatatcat           ttatgatctt               1981   tcctggtcaa aagatgatca ctacatcctt acttcatcat ctgatggcac           tgccaggata               2041   tggaaaaatg aaataaacaa tacaaatact ttcagagttt tacctcatcc           ttcttttgtt               2101   tacacggcta aattccatcc agctgtaaga gagctagtag ttacaggatg           ctatgattcc               2161   atgatacgga tatggaaagt tgagatgaga gaagattctg ccatattggt           ccgacagttt               2221   gatgttcaca aaagttttat caactcactt tgttttgata ctgaaggtca           tcatatgtat               2281   tcaggagatt gtacaggggt gattgttgtt tggaatacct atgtcaagat           taatgatttg               2341   gaacattcag tgcaccactg gactataaat aaggaaatta aagaaactga           gtttaaggga               2401   attccaataa gttatttgga gattcatccc aatggaaaac gtttgttaat           ccataccaaa               2461   gacagtactt tgagaattat ggatctccgg atattagtag caaggaagtt           tgtaggagca               2521   gcaaattatc gggagaagat tcatagtact ttgactccat gtgggacttt           tctgtttgct               2581   ggaagtgagg atggtatagt gtatgtttgg aacccagaaa caggagaaca           agtagccatg               2641   tattctgact tgccattcaa gtcacccatt cgagacattt cttatcatcc           atttgaaaat               2701   atggttgcat tctgtgcatt tgggcaaaat gagccaattc ttctgtatat           ttacgatttc               2761   catgttgccc agcaggaggc tgaaatgttc aaacgctaca atggaacatt           tccattacct               2821   ggaatacacc aaagtcaaga tgccctatgt acctgtccaa aactacccca           tcaaggctct               2881   tttcagattg atgaatttgt ccacactgaa agttcttcaa cgaagatgca           gctagtaaaa               2941   cagaggcttg aaactgtcac agaggtgata cgttcctgtg ctgcaaaagt           caacaaaaat               3001   ctctcattta cttcaccacc agcagtttcc tcacaacagt ctaagttaaa           gcagtcaaac               3061   atgctgaccg ctcaagagat tctacatcag tttggtttca ctcagaccgg           gattatcagc               3121   atagaaagaa agccttgtaa ccatcaggta gatacagcac caacggtagt           ggctctttat               3181   gactacacag cgaatcgatc agatgaacta accatccatc gcggagacat           tatccgagtg               3241   tttttcaaag ataatgaaga ctggtggtat ggcagcatag gaaagggaca           ggaaggttat               3301   tttccagcta atcatgtggc tagtgaaaca ctgtatcaag aactgcctcc           tgagataaag               3361   gagcgatccc ctcctttaag ccctgaggaa aaaactaaaa tagaaaaatc           tccagctcct               3421   caaaagcaat caatcaataa gaacaagtcc caggacttca gactaggctc           agaatctatg               3481   acacattctg aaatgagaaa agaacagagc catgaggacc aaggacacat           aatggataca               3541   cggatgagga agaacaagca agcaggcaga aaagtcactc taatagagta a            
AHl1 Protein ( Homo sapiens )
 
         [0000]                              SEQ ID NO: 10            1   mptaeseakv ktkvrfeell kthsdlmrek kklkkklvrs           eenispdtir snlhymkett               61   sddpdtirsn lphikettsd dvsaantnnl kkstrvtknk           lrntqlaten pngdasveed               121   kqgkpnkkvi ktvpqlttqd lkpetpenkv dsthqkthtk           pqpgvdhqks ekanegreet               181   dleedeelmq ayqchvteem akeikrkirk klkeqltyfp           sdtlfhddkl ssekrkkkke               241   vpvfskaets tltisgdtve geqkkessvr svssdshqdd           eissmeqste dsmqddtkpk               301   pkktkkktka vadnnedvdg dgvheitsrd spvypkclld           ddlvlgvyih rtdrlksdfm               361   ishpmvkihv vdehtgqyvk kddsgrpvss yyekenvdyi           lpimtqpydf kqlksrlpew               421   eeqivfnenf pyllrgsdes pkvilffeil dflsvdeikn           nsevqnqecg frkiawaflk               481   llgangnani nsklrlqlyy pptkprspls vveafewwsk           cprnhypstl yvtvrglkvp               541   dcikpsyrsm malqeekgkp vhcerhhess svdtepglee           skevikwkrl pgqacripnk               601   hlfslnager gcfcldfshn grilaaacas rdgypiilye           ipsgrfmrel cghlniiydl               661   swskddhyil tsssdgtari wkneinntnt frvlphpsfv           ytakfhpavr elvvtgcyds               721   miriwkvemr edsailvrqf dvhksfinsl cfdteghhmy           sgdctgvivv wntyvkindl               781   ehsvhhwtin keiketefkg ipisyleihp ngkrllihtk           dstlrimdlr ilvarkfvga               841   anyrekihst ltpcgtflfa gsedgivyvw npetgeqvam           ysdlpfkspi rdisyhpfen               901   mvafcafgqn epillyiydf hvaqqeaemf kryngtfplp           gihqsqdalc tcpklphqgs               961   fqidefvhte ssstkmqlvk qrletvtevi rscaakvnkn           lsftsppavs sqqsklkqsn               1021   mltaqeilhq fgftqtgiis ierkpcnhqv dtaptvvaly           dytanrsdel tihrgdiirv               1081   ffkdnedwwy gsigkgqegy fpanhvaset lyqelppeik           erspplspee ktkiekspap               1141   qkqsinknks qdfrlgsesm thsemrkeqs hedqghimdt           rmrknkqagr kvtlie            
Runx1 cDNA ( Homo sapiens )
 
         [0000]                              SEQ ID NO: 11            1   atggcttcag acagcatatt tgagtcattt ccttcgtacc           cacagtgctt catgagagaa               61   tgcatacttg gaatgaatcc ttctagagac gtccacgatg           ccagcacgag ccgccgcttc               121   acgccgcctt ccaccgcgct gagcccaggc aagatgagcg           aggcgttgcc gctgggcgcc               181   ccggacgccg gcgctgccct ggccggcaag ctgaggagcg           gcgaccgcag catggtggag               241   gtgctggccg accacccggg cgagctggtg cgcaccgaca           gccccaactt cctctgctcc               301   gtgctgccta cgcactggcg ctgcaacaag accctgccca           tcgctttcaa ggtggtggcc               361   ctaggggatg ttccagatgg cactctggtc actgtgatgg           ctggcaatga tgaaaactac               421   tcggctgagc tgagaaatgc taccgcagcc atgaagaacc           aggttgcaag atttaatgac               481   ctcaggtttg tcggtcgaag tggaagaggg aaaagcttca           ctctgaccat cactgtcttc               541   acaaacccac cgcaagtcgc cacctaccac agagccatca           aaatcacagt ggatgggccc               601   cgagaacctc gaagacatcg gcagaaacta gatgatcaga           ccaagcccgg gagcttgtcc               661   ttttccgagc ggctcagtga actggagcag ctgcggcgca           cagccatgag ggtcagccca               721   caccacccag cccccacgcc caaccctcgt gcctccctga           accactccac tgcctttaac               781   cctcagcctc agagtcagat gcaggataca aggcagatcc           aaccatcccc accgtggtcc               841   tacgatcagt cctaccaata cctgggatcc attgcctctc           cttctgtgca cccagcaacg               901   cccatttcac ctggacgtgc cagcggcatg acaaccctct           ctgcagaact ttccagtcga               961   ctctcaacgg cacccgacct gacagcgttc agcgacccgc           gccagttccc cgcgctgccc               1021   tccatctccg acccccgcat gcactatcca ggcgccttca           cctactcccc gacgccggtc               1081   acctcgggca tcggcatcgg catgtcggcc atgggctcgg           ccacgcgcta ccacacctac               1141   ctgccgccgc cctaccccgg ctcgtcgcaa gcgcagggag           gcccgttcca agccagctcg               1201   ccctcctacc acctgtacta cggcgcctcg gccggctcct           accagttctc catggtgggc               1261   ggcgagcgct cgccgccgcg catcctgccg ccctgcacca           acgcctccac cggctccgcg               1321   ctgctcaacc ccagcctccc gaaccagagc gacgtggtgg           aggccgaggg cagccacagc               1381   aactccccca ccaacatggc gccctccgcg cgcctggagg           aggccgtgtg gaggccctac               1441   tga            
RUNX1 Protein ( Homo sapiens )
 
         [0000]                              SEQ ID NO: 12            1   masdsifesf psypqcfmre cilgmnpsrd vhdastsrrf           tppstalspg kmsealplga               61   pdagaalagk lrsgdrsmve vladhpgelv rtdspnflcs           vlpthwrcnk tlpiafkvva               121   lgdvpdgtlv tvmagndeny saelrnataa mknqvarfnd           lrfvgrsgrg ksftltitvf               181   tnppqvatyh raikitvdgp reprrhrqkl ddqtkpgsls           fserlseleq lrrtamrvsp               241   hhpaptpnpr aslnhstafn pqpqsqmqdt rqiqpsppws           ydqsyqylgs iaspsvhpat               301   pispgrasgm ttlsaelssr lstapdltaf sdprqfpalp           sisdprmhyp gaftysptpv               361   tsgigigmsa mgsatryhty lpppypgssq aqggpfqass           psyhlyygas agsyqfsmvg               421   gerspprilp pctnastgsa llnpslpnqs dvveaegshs           nsptnmapsa rleeavwrpy            
Ets2 cDNA ( Homo sapiens )
 
         [0000]                              SEQ ID NO: 13            1   atgaatgatt tcggaatcaa gaatatggac caggtagccc           ctgtggctaa cagttacaga               61   gggacactca agcgccagcc agcctttgac acctttgatg           ggtccctgtt tgctgttttt               121   ccttctctaa atgaagagca aacactgcaa gaagtgccaa           caggcttgga ttccatttct               181   catgactccg ccaactgtga attgcctttg ttaaccccgt           gcagcaaggc tgtgatgagt               241   caagccttaa aagctacctt cagtggcttc aaaaaggaac           agcggcgcct gggcattcca               301   aagaacccct ggctgtggag tgagcaacag gtatgccagt           ggcttctctg ggccaccaat               361   gagttcagtc tggtgaacgt gaatctgcag aggttcggca           tgaatggcca gatgctgtgt               421   aaccttggca aggaacgctt tctggagctg gcacctgact           ttgtgggtga cattctctgg               481   gaacatctgg agcaaatgat caaagaaaac caagaaaaga           cagaagatca atatgaagaa               541   aattcacacc tcacctccgt tcctcattgg attaacagca           atacattagg ttttggcaca               601   gagcaggcgc cctatggaat gcagacacag aattacccca           aaggcggcct cctggacagc               661   atgtgtccgg cctccacacc cagcgtactc agctctgagc           aggagtttca gatgttcccc               721   aagtctcggc tcagctccgt cagcgtcacc tactgctctg           tcagtcagga cttcccaggc               781   agcaacttga atttgctcac caacaattct gggactccca           aagaccacga ctcccctgag               841   aacggtgcgg acagcttcga gagctcagac tccctcctcc           agtcctggaa cagccagtcg               901   tccttgctgg atgtgcaacg ggttccttcc ttcgagagct           tcgaagatga ctgcagccag               961   tctctctgcc tcaataagcc aaccatgtct ttcaaggatt           acatccaaga gaggagtgac               1021   ccagtggagc aaggcaaacc agttatacct gcagctgtgc           tggccggctt cacaggaagt               1081   ggacctattc agctgtggca gtttctcctg gagctgctat           cagacaaatc ctgccagtca               1141   ttcatcagct ggactggaga cggatgggag tttaagctcg           ccgaccccga tgaggtggcc               1201   cgccggtggg gaaagaggaa aaataagccc aagatgaact           acgagaagct gagccggggc               1261   ttacgctact attacgacaa gaacatcatc cacaagacgt           cggggaagcg ctacgtgtac               1321   cgcttcgtgt gcgacctcca gaacttgctg gggttcacgc           ccgaggaact gcacgccatc               1381   ctgggcgtcc agcccgacac ggaggactga            
ETS2 Protein ( Homo sapiens )
 
         [0000]                              SEQ ID NO: 14            1   mndfgiknmd qvapvansyr gtlkrqpafd tfdgslfavf           pslneeqtlq evptgldsis               61   hdsancelpl ltpcskavms qalkatfsgf kkeqrrlgip           knpwlwseqq vcqwllwatn               121   efslvnvnlq rfgmngqmlc nlgkerflel apdfvgdilw           ehleqmiken qektedgyee               181   nshltsvphw insntlgfgt eqapygmqtq nypkggllds           mcpastpsvl sseqefqmfp               241   ksrlssvsvt ycsvsqdfpg snlnlltnns gtpkdhdspe           ngadsfessd sllqswnsqs               301   slldvqrvps fesfeddcsq slclnkptms fkdyiqersd           pveqgkpvip aavlagftgs               361   gpiqlwqfll ellsdkscqs fiswtgdgwe fkladpdeva           rrwgkrknkp kmnyeklsrg               421   lryyydknii hktsgkryvy rfvcdlqnll gftpeelhai           lgvqpdted            
Tmprss2 cDNA ( Homo sapiens )
 
         [0000]                              SEQ ID NO: 15            1   atggctttga actcagggtc accaccagct attggacctt           actatgaaaa ccatggatac               61   caaccggaaa acccctatcc cgcacagccc actgtggtcc           ccactgtcta cgaggtgcat               121   ccggctcagt actacccgtc ccccgtgccc cagtacgccc           cgagggtcct gacgcaggct               181   tccaaccccg tcgtctgcac gcagcccaaa tccccatccg           ggacagtgtg cacctcaaag               241   actaagaaag cactgtgcat caccttgacc ctggggacct           tcctcgtggg agctgcgctg               301   gccgctggcc tactctggaa gttcatgggc agcaagtgct           ccaactctgg gatagagtgc               361   gactcctcag gtacctgcat caacccctct aactggtgtg           atggcgtgtc acactgcccc               421   ggcggggagg acgagaatcg gtgtgttcgc ctctacggac           caaacttcat ccttcagatg               481   tactcatctc agaggaagtc ctggcaccct gtgtgccaag           acgactggaa cgagaactac               541   gggcgggcgg cctgcaggga catgggctat aagaataatt           tttactctag ccaaggaata               601   gtggatgaca gcggatccac cagctttatg aaactgaaca           caagtgccgg caatgtcgat               661   atctataaaa aactgtacca cagtgatgcc tgttcttcaa           aagcagtggt ttctttacgc               721   tgtatagcct gcggggtcaa cttgaactca agccgccaga           gcaggatcgt gggcggtgag               781   agcgcgctcc cgggggcctg gccctggcag gtcagcctgc           acgtccagaa cgtccacgtg               841   tgcggaggct ccatcatcac ccccgagtgg atcgtgacag           ccgcccactg cgtggaaaaa               901   cctcttaaca atccatggca ttggacggca tttgcgggga           ttttgagaca atctttcatg               961   ttctatggag ccggatacca agtagaaaaa gtgatttctc           atccaaatta tgactccaag               1021   accaagaaca atgacattgc gctgatgaag ctgcagaagc           ctctgacttt caacgaccta               1081   gtgaaaccag tgtgtctgcc caacccaggc atgatgctgc           agccagaaca gctctgctgg               1141   atttccgggt ggggggccac cgaggagaaa gggaagacct           cagaagtgct gaacgctgcc               1201   aaggtgcttc tcattgagac acagagatgc aacagcagat           atgtctatga caacctgatc               1261   acaccagcca tgatctgtgc cggcttcctg caggggaacg           tcgattcttg ccagggtgac               1321   agtggagggc ctctggtcac ttcgaagaac aatatctggt           ggctgatagg ggatacaagc               1381   tggggttctg gctgtgccaa agcttacaga ccaggagtgt           acgggaatgt gatggtattc               1441   acggactgga tttatcgaca aatgagggca gacggctaa            
TMPRSS2 Protein ( Homo sapiens )
 
         [0000]                              SEQ ID NO: 16            1   malnsgsppa igpyyenhgy qpenpypaqp tvvptvyevh           paqyypspvp qyaprvltqa               61   snpvvctqpk spsgtvctsk tkkalcitlt lgtflvgaal           aagllwkfmg skcsnsgiec               121   dssgtcinps nwcdgvshcp ggedenrcvr lygpnfilqm           yssqrkswhp vcqddwneny               181   graacrdmgy knnfyssqgi vddsgstsfm klntsagnvd           iykklyhsda csskavvslr               241   ciacgvnlns srqsrivgge salpgawpwq vslhvqnvhv           cggsiitpew ivtaahcvek               301   plnnpwhwta fagilrqsfm fygagyqvek vishpnydsk           tknndialmk lqkpltfndl               361   vkpvclpnpg mmlqpeqlcw isgwgateek gktsevlnaa           kvllietqrc nsryvydnli               421   tpamicagfl qgnvdscqgd sggplvtskn niwwligdts           wgsgcakayr pgvygnvmvf               481   tdwiyrqmra dg            
Ripk4 cDNA ( Homo sapiens )
 
         [0000]                                      SEQ ID NO: 17                1   atggagggcg acggcgggac cccatgggcc ctggcgctgc tgcgcacctt cgacgcgggc                   61   gagttcacgg gctgggagaa ggtgggctcg ggcggcttcg ggcaggtgta           caaggtgcgc               121   catgtccact ggaagacctg gctggccatc aagtgctcgc ccagcctgca cgtcgacgac               181   agggagcgca tggagctttt ggaagaagcc aagaagatgg agatggccaa           gtttcgctac               241   atcctgcctg tgtatggcat ctgccgcgaa cctgtcggcc tggtcatgga gtacatggag               301   acgggctccc tggaaaagct gctggcttcg gagccattgc catgggatct           ccggttccga               361   atcatccacg agacggcggt gggcatgaac ttcctgcact gcatggcccc           gccactcctg               421   cacctggacc tcaagcccgc gaacatcctg ctggatgccc actaccacgt           caagatttct               481   gattttggtc tggccaagtg caacgggctg tcccactcgc atgacctcag catggatggc               541   ctgtttggca caatcgccta cctccctcca gagcgcatca gggagaagag           ccggctcttc               601   gacaccaagc acgatgtata cagctttgcg atcgtcatct ggggcgtgct           cacacagaag               661   aagccgtttg cagatgagaa gaacatcctg cacatcatgg tgaaggtggt           gaagggccac               721   cgccccgagc tgccgcccgt gtgcagagcc cggccgcgcg cctgcagcca           cctgatacgc               781   ctcatgcagc ggtgctggca gggggatccg cgagttaggc ccaccttcca           agaaattact               841   tctgaaaccg aggacctgtg tgaaaagcct gatgacgaag tgaaagaaac           tgctcatgat               901   ctggacgtga aaagcccccc ggagcccagg agcgaggtgg tgcctgcgag           gctcaagcgg               961   gcctctgccc ccaccttcga taacgactac agcctctccg agctgctctc acagctggac               1021   tctggagttt cccaggctgt cgagggcccc gaggagctca gccgcagctc           ctctgagtcc               1081   aagctgccat cgtccggcag tgggaagagg ctctcggggg tgtcctcggt           ggactccgcc               1141   ttctcttcca gaggatcact gtcgctgtcc tttgagcggg aaccttcaac cagcgatctg               1201   ggcaccacag acgtccagaa gaagaagctt gtggatgcca tcgtgtccgg ggacaccagc               1261   aaactgatga agatcctgca gccgcaggac gtggacctgg cactggacag           cggtgccagc               1321   ctgctgcacc tggcggtgga ggccgggcaa gaggagtgcg ccaagtggct gctgctcaac               1381   aatgccaacc ccaacctgag caaccgtagg ggctccaccc cgttgcacat           ggccgtggag               1441   aggagggtgc ggggtgtcgt ggagctcctg ctggcgcgga agatcagtgt caacgccaag               1501   gatgaggacc agtggacagc cctccacttt gcagcccaga acggggacga           gtctagcaca               1561   cggctgctgt tggagaagaa cgcctcggtc aacgaggtgg actttgaggg           ccggacgccc               1621   atgcacgtgg cctgccagca cgggcaggag aatatcgtgc gcatcctgct gcgccgaggc               1681   gtggacgtga gcctgcaggg caaggatgcc tggctgccac tgcactacgc           tgcctggcag               1741   ggccacctgc ccatcgtcaa gctgctggcc aagcagccgg gggtgagtgt gaacgcccag               1801   acgctggatg ggaggacgcc attgcacctg gccgcacagc gcgggcacta           ccgcgtggcc               1861   cgcatcctca tcgacctgtg ctccgacgtc aacgtctgca gcctgctggc acagacaccc               1921   ctgcacgtgg ccgcggagac ggggcacacg agcactgcca ggctgctcct           gcatcggggc               1981   gctggcaagg aggccatgac ctcagacggc tacaccgctc tgcacctggc tgcccgcaac               2041   ggacacctgg ccactgtcaa gctgcttgtc gaggagaagg ccgatgtgct           ggcccgggga               2101   cccctgaacc agacggcgct gcacctggct gccgcccacg ggcactcgga           ggtggtggag               2161   gagttggtca gcgccgatgt cattgacctg ttcgacgagc aggggctcag cgcgctgcac               2221   ctggccgccc agggccggca cgcacagacg gtggagactc tgctcaggca           tggggcccac               2281   atcaacctgc agagcctcaa gttccagggc ggccatggcc ccgccgccac gctcctgcgg               2341   cgaagcaaga cctag            
RIPK4 Protein ( Homo sapiens )
 
         [0000]                              SEQ ID NO: 18            1   megdggtpwa lallrtfdag eftgwekvgs ggfgqvykvr           hvhwktwlai kcspslhvdd               61   rermelleea kkmemakfry ilpvygicre pvglvmeyme           tgslekllas eplpwdlrfr               121   iihetavgmn flhcmappll hldlkpanil ldahyhvkis           dfglakcngl shshdlsmdg               181   lfgtiaylpp erireksrlf dtkhdvysfa iviwgvltqk           kpfadeknil himvkvvkgh               241   rpelppvcra rpracshlir lmqrcwqgdp rvrptfqeit           setedlcekp ddevketahd               301   ldvksppepr sevvparlkr asaptfdndy slsellsqld           sgvsqavegp eelsrssses               361   klpssgsgkr lsgvssvdsa fssrgslsls ferepstsdl           gttdvqkkkl vdaivsgdts               421   klmkilqpqd vdlaldsgas llhlaveagq eecakwllln           nanpnlsnrr gstplhmave               481   rrvrgvvell larkisvnak dedqwtalhf aaqngdesst           rllleknasv nevdfegrtp               541   mhvacqhgqe nivrillrrg vdvslqgkda wlplhyaawq           ghlpivklla kqpgvsvnaq               601   tldgrtplhl aaqrghyrva rilidlcsdv nvcsllaqtp           lhvaaetght starlllhrg               661   agkeamtsdg ytalhlaarn ghlatvkllv eekadvlarg           plnqtalhla aahghsevve               721   elvsadvidl fdeqglsalh laaqgrhaqt vetllrhgah           inlqslkfqg ghgpaatllr               781   rskt            
Erg cDNA ( Homo sapiens )
 
         [0000]                              SEQ ID NO: 19            1   atggccagca ctattaagga agccttatca gttgtgagtg           aggaccagtc gttgtttgag               61   tgtgcctacg gaacgccaca cctggctaag acagagatga           ccgcgtcctc ctccagcgac               121   tatggacaga cttccaagat gagcccacgc gtccctcagc           aggattggct gtctcaaccc               181   ccagccaggg tcaccatcaa aatggaatgt aaccctagcc           aggtgaatgg ctcaaggaac               241   tctcctgatg aatgcagtgt ggccaaaggc gggaagatgg           tgggcagccc agacaccgtt               301   gggatgaact acggcagcta catggaggag aagcacatgc           cacccccaaa catgaccacg               361   aacgagcgca gagttatcgt gccagcagat cctacgctat           ggagtacaga ccatgtgcgg               421   cagtggctgg agtgggcggt gaaagaatat ggccttccag           acgtcaacat cttgttattc               481   cagaacatcg atgggaagga actgtgcaag atgaccaagg           acgacttcca gaggctcacc               541   cccagctaca acgccgacat ccttctctca catctccact            acctcagaga gactcctctt               601   ccacatttga cttcagatga tgttgataaa gccttacaaa           actctccacg gttaatgcat               661   gctagaaaca cagggggtgc agcttttatt ttcccaaata           cttcagtata tcctgaagct               721   acgcaaagaa ttacaactag gccagattta ccatatgagc           cccccaggag atcagcctgg               781   accggtcacg gccaccccac gccccagtcg aaagctgctc           aaccatctcc ttccacagtg               841   cccaaaactg aagaccagcg tcctcagtta gatccttatc           agattcttgg accaacaagt               901   agccgccttg caaatccagg cagtggccag atccagcttt           ggcagttcct cctggagctc               961   ctgtcggaca gctccaactc cagctgcatc acctgggaag           gcaccaacgg ggagttcaag               1021   atgacggatc ccgacgaggt ggcccggcgc tggggagagc           ggaagagcaa acccaacatg               1081   aactacgata agctcagccg cgccctccgt tactactatg           acaagaacat catgaccaag               1141   gtccatggga agcgctacgc ctacaagttc gacttccacg           ggatcgccca ggccctccag               1201   ccccaccccc cggagtcatc tctgtacaag tacccctcag           acctcccgta catgggctcc               1261   tatcacgccc acccacagaa gatgaacttt gtggcgcccc           accctccagc cctccccgtg               1321   acatcttcca gtttttttgc tgccccaaac ccatactgga           attcaccaac tgggggtata               1381   taccccaaca ctaggctccc caccagccat atgccttctc           atctgggcac ttactactaa            
ERG Protein ( Homo sapiens )
 
         [0000]                              SEQ ID NO: 20            1   mastikeals vvsedqslfe caygtphlak temtassssd           ygqtskmspr vpqqdwlsqp               61   parvtikmec npsqvngsrn spdecsvakg gkmvgspdtv           gmnygsymee khmpppnmtt               121   nerrvivpad ptlwstdhvr qwlewavkey glpdvnillf           qnidgkelck mtkddfqrlt               181   psynadills hlhylretpl phltsddvdk alqnsprlmh           arntggaafi fpntsvypea               241   tqrittrpdl pyepprrsaw tghghptpqs kaaqpspstv           pktedqrpql dpyqilgpts               301   srlanpgsgq iqlwqfllel lsdssnssci twegtngefk           mtdpdevarr wgerkskpnm               361   nydklsralr yyydknimtk vhgkryaykf dfhgiaqalq           phppesslyk ypsdlpymgs               421   yhahpqkmnf vaphppalpv tsssffaapn pywnsptggi           ypntrlptsh mpshlgtyy            
Gnb2 cDNA ( Homo sapiens )
 
         [0000]                              SEQ ID NO: 21            1   atgagtgagc tggagcaact gagacaggag gccgagcagc           tccggaacca gatccgggat               61   gcccgaaaag catgtgggga ctcaacactg acccagatca           cagctgggct ggacccagtg               121   gggagaatcc agatgaggac ccggaggacc ctccgtgggc           acctggcaaa gatctatgcc               181   atgcactggg ggaccgactc aaggctgctg gtcagcgcct           cccaggatgg gaagctcatc               241   atctgggaca gctacaccac caacaaggtc cacgccatcc           cgctgcgctc ctcctgggta               301   atgacctgtg cctacgcgcc ctcagggaac tttgtggcct           gtggggggtt ggacaacatc               361   tgctccatct acagcctcaa gacccgcgag ggcaacgtca           gggtcagccg ggagctgcct               421   ggccacactg ggtacctgtc gtgttgccgc ttcctggatg           acaaccaaat catcaccagc               481   tctggggata ccacctgtgc cctgtgggac attgagacag           gccagcagac agtgggtttt               541   gctggacaca gtggggatgt gatgtccctg tccctggccc           ccgatggccg cacgtttgtg               601   tcaggcgcct gtgatgcctc tatcaagctg tgggacgtgc           gggattccat gtgccgacag               661   accttcatcg gccatgaatc cgacatcaat gcagtggctt           tcttccccaa cggctacgcc               721   ttcaccaccg gctctgacga cgccacgtgc cgcctcttcg           acctgcgggc cgatcaggag               781   ctcctcatgt actcccatga caacatcatc tgtggcatca           cctctgttgc cttctcgcgc               841   agcggacggc tgctgctcgc tggctacgac gacttcaact           gcaacatctg ggatgccatg               901   aagggcgacc gtgcaggagt cctcgctggc cacgacaacc           gcgtgagctg cctcggggtc               961   accgacgatg gcatggctgt ggccacgggc tcctgggact           ccttcctcaa gatctggaac               1021   taa            
GNB2 Protein ( Homo sapiens )
 
         [0000]                              SEQ ID NO: 22            1   mseleqlrqe aeqlrnqird arkacgdstl tqitagldpv           griqmrtrrt lrghlakiya               61   mhwgtdsrll vsasqdgkli iwdsyttnkv haiplrsswv           mtcayapsgn fvacggldni               121   csiyslktre gnvrvsrelp ghtgylsccr flddnqiits           sgdttcalwd ietgqqtvgf               181   aghsgdvmsl slapdgrtfv sgacdasikl wdvrdsmcrq           tfighesdin avaffpngya               241   fttgsddatc rlfdlradqe llmyshdnii cgitsvafsr           sgrlllagyd dfncniwdam               301   kgdragvlag hdnrvsclgv tddgmavatg swdsflkiwn            
Perq1 cDNA ( Homo sapiens )
 
         [0000]                                      SEQ ID NO: 23                1   atggcagcag agacactcaa ctttgggcct gagtggctca gggccctgtc cgggggcggc                   61   agcgtggcct ccccaccccc gtcccctgcc atgcccaaat acaagctggc           tgactaccgt               121   tatgggcgag aggaaatgct ggctctctac gtcaaggaga acaaggtccc ggaagagctg               181   caggacaagg agttcgccgc ggtgctgcag gacgagccac tgcagcccct           ggctctggag               241   ccgctgactg aggaggaaca gagaaacttc tccctgtcag tgaacagcgt ggctgtgctg               301   aggctgatgg ggaaaggggc tggccccccc ctggctggca cctcccgagg           caggggcagc               361   acgcggagcc gaggccgcgg ccgtggtgac agctgctttt accaaagaag catcgaagaa               421   ggcgatgggg cctttggacg aagcccccgg gaaatccagc gcagccagag           ctgggatgac               481   agaggcgaga ggcggtttga gaagtcagca aggcgggatg gagcacgatg           tggctttgag               541   gagggagggg ctggcccaag gaaggagcac gcccgctcag acagcgagaa           ctggcgctcc               601   ctacgggagg aacaggagga ggaggaggag ggcagctgga ggctcggagc           agggccccgg               661   cgagacggcg accgctggcg ctccgccagc cctgatggtg gtccccgctc tgctggctgg               721   cgggaacatg gggaacggcg gcgcaagttt gaatttgatt tgcgagggga tcgaggaggg               781   tgtggtgaag aggaggggcg gggaggggga ggcagctctc acctgcggcg           gtgccgagcg               841   cctgaaggct ttgaggagga caaggatggg ctcccagagt ggtgcctgga cgatgaggat               901   gaagaaatgg gcacctttga tgcctctggg gccttcttgc ctctcaagaa gggccccaag               961   gagcccattc ctgaggagca ggagctggac ttccaagggt tggaggagga ggaggaacct               1021   tccgaagggc tagaggagga agggcctgag gcaggtggga aagagctgac           cccactgcct               1081   cctcaggagg agaagtccag ctccccatcc ccactgccca ccctgggccc           actctggggg               1141   acaaacgggg atggggacga aactgcagag aaagagcccc cagcggccga           agatgatatt               1201   cgggggatcc agctgagtcc cggggtgggc tcctctgctg gcccacccgg           agatctggag               1261   gatgatgaag gcttgaagca cctgcagcag gaggcggaga agctggtggc           ctccctgcag               1321   gacagctcct tggaggagga gcagttcacg gctgccatgc agacccaggg           cctgcgccac               1381   tctgcagccg ccactgccct cccgctcagc catggggctg cccggaagtg gttctacaag               1441   gacccacagg gcgagatcca aggccccttc acgacacagg agatggcaga           gtggttccag               1501   gccggctact tttccatgtc actgctggtg aagcggggct gcgatgaggg cttccagccg               1561   ctgggcgagg tgatcaagat gtggggccgc gtgccctttg ccccagggcc ctcacctccc               1621   ccactgctgg gaaacatgga ccaggagcgg ctgaagaagc aacaggagct           ggccgcggcg               1681   gccttgtacc agcagctgca gcaccagcag tttctccagc tggtcagcag ccgccagctc               1741   ccgcagtgcg cgctccgaga aaaggcagct ctgggggacc tgacaccgcc           accaccgccg               1801   ccgccacagc agcagcagca gcagctcacg gcattcctgc agcagctcca           ggcgctcaaa               1861   ccccccagag gcggggacca gaacctgctc ccgacgatga gccggtcctt gtcggtgcca               1921   gattcgggcc gcctctggga cgtacatacc tcagcctcat cacagtcagg tggtgaggcc               1981   agtctttggg acataccaat taactcttcg actcagggtc caattctaga acaactccag               2041   ctgcaacata aattccagga gcgcagagaa gtggagctca gggcgaagcg           ggaggaagag               2101   gaacgcaagc gtcgagagga gaagcgccgc cagcagcagc aggaggagca           gaagcggcgg               2161   caggaggagg aagagctgtt tcggcgcaag cacgtgcggc agcaggagct           attgctgaag               2221   ttgctacagc agcagcaggc ggtccctgtg ccccccgcac ccagctcccc gcccccactc               2281   tgggctggcc tggccaagca ggggctgtcc atgaagacgc tcctggagtt gcagctggag               2341   ggcgagcggc agctgcacaa acagccccca cctcgggagc cagctcgggc           ccaggccccc               2401   aaccaccgag tgcagcttgg gggcctgggc actgcccccc tgaaccagtg           ggtgtctgag               2461   gctgggccac tgtggggcgg gccagacaag agtgggggcg gcagcagcgg           cctggggctc               2521   tgggaggaca cccccaagag cggcgggagc ctggtccgtg gcctcggcct           gaagaacagc               2581   cggagcagcc catctctcag tgactcatac agccacctat cgggtcggcc cattcgcaaa               2641   aagacggagg aagaagagaa gctgctgaag ctgctgcagg gcattcccag           gccccaggac               2701   ggcttcaccc agtggtgcga gcagatgctg cacacgctga gcgccacggg cagcctggac               2761   gtgcccatgg ctgtagcgat cctcaaggag gtggaatccc cctatgatgt ccacgattat               2821   atccgttcct gcctggggga cacgctggaa gccaaagaat ttgccaaaca attcctggag               2881   cggagggcca agcagaaagc cagccagcag cggcagcagc agcaggaggc           atggctgagc               2941   agcgcctcgc tgcagacggc cttccaggcc aaccacagca ccaaactcgg           ccccggggag               3001   ggcagcaagg ccaagaggcg ggcactgatg ctgcactcag accccagcat           cctggggtac               3061   tccctgcacg gatcttctgg tgagatcgag agcgtggatg actactga            
PERQ1 Protein ( Homo sapiens )
 
         [0000]                              SEQ ID NO: 24            1   maaetlnfgp ewlralsggg svaspppspa mpkykladyr           ygreemlaly vkenkvpeel               61   qdkefaavlq deplqplale plteeeqrnf slsvnsvavl           rlmgkgagpp lagtsrgrgs               121   trsrgrgrgd scfyqrsiee gdgafgrspr eiqrsqswdd           rgerrfeksa rrdgarcgfe               181   eggagprkeh arsdsenwrs lreeqeeeee gswrlgagpr           rdgdrwrsas pdggprsagw               241   rehgerrrkf efdlrgdrgg cgeeegrggg gsshlrrcra           pegfeedkdg lpewcldded               301   eemgtfdasg aflplkkgpk epipeeqeld fqgleeeeep           segleeegpe aggkeltplp               361   pqeeksssps plptlgplwg tngdgdetae keppaaeddi           rgiqlspgvg ssagppgdle               421   ddeglkhlqq eaeklvaslq dssleeeqft aamqtqglrh           saaatalpls hgaarkwfyk               481   dpqgeiqgpf ttqemaewfq agyfsmsllv krgcdegfqp           lgevikmwgr vpfapgpspp               541   pllgnmdqer lkkqqelaaa alyqqlqhqq flqlvssrql           pqcalrekaa lgdltppppp               601   ppqqqqqqlt aflqqlqalk pprggdqnll ptmsrslsvp           dsgrlwdvht sassqsggea               661   slwdipinss tqgpileqlq lqhkfqerre velrakreee           erkrreekrr qqqqeeqkrr               721   qeeeelfrrk hvrqqelllk llqqqqavpv ppapsspppl           waglakqgls mktllelqle               781   gerqlhkqpp preparaqap nhrvqlgglg taplnqwvse           agplwggpdk sgggssglgl               841   wedtpksggs lvrglglkns rsspslsdsy shlsgrpirk           kteeeekllk llqgiprpqd               901   gftqwceqml htlsatgsld vpmavailke vespydvhdy           irsclgdtle akefakqfle               961   rrakqkasqq rqqqqeawls saslqtafqa nhstklgpge           gskakrralm lhsdpsilgy               1021   slhgssgeie svddy            
Tox cDNA ( Homo sapiens )
 
         [0000]                                      SEQ ID NO: 25                1   atggacgtaa gattttatcc acctccagcc cagcccgccg ctgcgcccga               cgctccctgt               61   ctgggacctt ctccctgcct ggacccctac tattgcaaca agtttgacgg           tgagaacatg               121   tatatgagca tgacagagcc gagccaggac tatgtgccag ccagccagtc           ctaccctggt               181   ccaagcctgg aaagtgaaga cttcaacatt ccaccaatta ctcctccttc           cctcccagac               241   cactcgctgg tgcacctgaa tgaagttgag tctggttacc attctctgtg           tcaccccatg               301   aaccataatg gcctgctacc atttcatcca caaaacatgg acctccctga           aatcacagtc               361   tccaatatgc tgggccagga tggaacactg ctttctaatt ccatttctgt           gatgccagat               421   atacgaaacc cagaaggaac tcagtacagt tcccatcctc agatggcagc           catgagacca               481   aggggccagc ctgcagacat caggcagcag ccaggaatga tgccacatgg           ccagctgact               541   accattaacc agtcacagct aagtgctcaa cttggtttga atatgggagg           aagcaatgtt               601   ccccacaact caccatctcc acctggaagc aagtctgcaa ctccttcacc           atccagttca               661   gtgcatgaag atgaaggcga tgatacctct aagatcaatg gtggagagaa           gcggcctgcc               721   tctgatatgg ggaaaaaacc aaaaactccc aaaaagaaga agaagaagga           tcccaatgag               781   ccccagaagc ctgtgtctgc ctatgcgtta ttctttcgtg atactcaggc           cgccatcaag               841   ggccaaaatc caaacgctac ctttggcgaa gtctctaaaa ttgtggcttc           aatgtgggac               901   ggtttaggag aagagcaaaa acaggtctat aaaaagaaaa ccgaggctgc           gaagaaggag               961   tacctgaagc aactcgcagc atacagagcc agccttgtat ccaagagcta           cagtgaacct               1021   gttgacgtga agacatctca acctcctcag ctgatcaatt cgaagccgtc           ggtgttccat               1081   gggcccagcc aggcccactc ggccctgtac ctaagttccc actatcacca           acaaccggga               1141   atgaatcctc acctaactgc catgcatcct agtctcccca ggaacatagc           ccccaagccg               1201   aataaccaaa tgccagtgac tgtctctata gcaaacatgg ctgtgtcccc           tcctcctccc               1261   ctccagatca gcccgcctct tcaccagcat ctcaacatgc agcagcacca           gccgctcacc               1321   atgcagcagc cccttgggaa ccagctcccc atgcaggtcc agtctgcctt           acactcaccc               1381   accatgcagc aaggatttac tcttcaaccc gactatcaga ctattatcaa           tcctacatct               1441   acagctgcac aagttgtcac ccaggcaatg gagtatgtgc gttcggggtg           cagaaatcct               1501   cccccacaac cggtggactg gaataacgac tactgcagta gtgggggcat           gcagagggac               1561   aaagcactgt accttacttg a            
TOX Protein ( Homo sapiens )
 
         [0000]                                      SEQ ID NO: 26                1   mdvrfypppa qpaaapdapc lgpspcldpy ycnkfdgenm ymsmtepsqd               yvpasqsypg               61   pslesedfni ppitppslpd hslvhlneve sgyhslchpm nhngllpfhp           qnmdlpeitv               121   snmlgqdgtl lsnsisvmpd irnpegtqys shpqmaamrp rggpadirqq           pgmmphgqlt               181   tinqsqlsaq lglnmggsnv phnspsppgs ksatpspsss vhedegddts           kinggekrpa               241   sdmgkkpktp kkkkkkdpne pqkpvsayal ffrdtqaaik gqnpnatfge           vskivasmwd               301   glgeeqkqvy kkkteaakke ylkqlaayra slvsksysep vdvktsqppq           linskpsvfh               361   gpsqahsaly lsshyhqqpg mnphltamhp slprniapkp nnqmpvtvsi           anmavspppp               421   lqispplhqh lnmqqhqplt mqqplgnqlp mqvqsalhsp tmqqgftlqp           dyqtiinpts               481   taaqvvtqam eyvrsgcrnp ppqpvdwnnd ycssggmqrd kalylt            
Set cDNA ( Homo sapiens )
 
         [0000]                                      SEQ ID NO: 27                1   atggccccta aacgccagtc tccactcccg cctcaaaaga agaaaccaag               accacctcct               61   gctctgggac cggaggagac atcggcctct gcaggcttgc cgaagaaggg           agaaaaagaa               121   cagcaagaag cgattgaaca cattgatgaa gtacaaaatg aaatagacag           acttaatgaa               181   caagccagtg aggagatttt gaaagtagaa cagaaatata acaaactccg           ccaaccattt               241   tttcagaaga ggtcagaatt gatcgccaaa atcccaaatt tttgggtaac           aacatttgtc               301   aaccatccac aagtgtctgc actgcttggg gaggaagatg aagaggcact           gcattatttg               361   accagagttg aagtgacaga atttgaagat attaaatcag gttacagaat           agatttttat               421   tttgatgaaa atccttactt tgaaaataaa gttctctcca aagaatttca           tctgaatgag               481   agtggtgatc catcttcgaa gtccaccgaa atcaaatgga aatctggaaa           ggatttgacg               541   aaacgttcga gtcaaacgca gaataaagcc agcaggaaga ggcagcatga           ggaaccagag               601   agcttcttta cctggtttac tgaccattct gatgcaggtg ctgatgagtt           aggagaggtc               661   atcaaagatg atatttggcc aaacccatta cagtactact tggttcccga           tatggatgat               721   gaagaaggag aaggagaaga agatgatgat gatgatgaag aggaggaagg           attagaagat               781   attgacgaag aaggggatga ggatgaaggt gaagaagatg aagatgatga           tgaaggggag               841   gaaggagagg aggatgaagg agaagatgac taa            
SET Protein ( Homo sapiens )
 
         [0000]                                      SEQ ID NO: 28                1   mapkrqsplp pqkkkprppp algpeetsas aglpkkgeke qqeaiehide               vqneidrlne               61   qaseeilkve qkynklrqpf fqkrseliak ipnfwvttfv nhpqvsallg           eedeealhyl               121   trvevtefed iksgyridfy fdenpyfenk vlskefhlne sgdpsskste           ikwksgkdlt               181   krssqtqnka srkrqheepe sfftwftdhs dagadelgev ikddiwpnpl           qyylvpdmdd               241   eegegeeddd ddeeeegled ideegdedeg eededddege egeedegedd            
Fnbp1 cDNA ( Homo sapiens )
 
         [0000]                                      SEQ ID NO: 29                1   atgagctggg gcaccgagct ctgggatcag tttgacaact tagaaaaaca               cacacagtgg               61   ggaattgata ttcttgagaa atatatcaag tttgtgaaag aaaggacaga           gattgaactc               121   agctatgcaa agcaactcag gaatctttca aagaagtacc aacctaaaaa           gaactcgaag               181   gaggaagaag aatacaagta tacgtcatgt aaagctttca tttccaacct           gaacgaaatg               241   aatgattacg cagggcagca tgaagttatc tccgagaaca tggcatcaca           gatcattgtg               301   gacttggcac gctatgttca ggaactgaaa caggagagga aatcaaactt           tcacgatggc               361   cgtaaagcac agcagcacat cgagacttgc tggaagcagc ttgaatctag           taaaaggcga               421   tttgaacgcg attgcaaaga ggcggacagg gcgcagcagt actttgagaa           aatggacgct               481   gacatcaatg tcacaaaagc ggatgttgaa aaggcccgac aacaagctca           aatacgtcac               541   caaatggcag aggacagcaa agcagattac tcatccattc tccagaaatt           caaccatgag               601   cagcatgaat attaccatac tcacatcccc aacatcttcc agaaaataca           agagatggag               661   gaaaggagga ttgtgagaat gggagagtcc atgaagacat atgcagaggt           tgatcggcag               721   gtgatcccaa tcattgggaa gtgcctggat ggaatagtaa aagcagccga           atcaattgat               781   cagaaaaatg attcacagct ggtaatagaa gcttataaat cagggtttga           gcctcctgga               841   gacattgaat ttgaggatta cactcagcca atgaagcgca ctgtgtcaga           taacagcctt               901   tcaaattcca gaggagaagg caaaccagac ctcaaatttg gtggcaaatc           caaaggaaag               961   ttatggccgt tcatcaaaaa aaataagctt atgtcccttt taacatcccc           ccatcagcct               1021   ccccctcccc ctcctgcctc tgcctcaccc tctgctgttc ccaacggccc           ccagtctccc               1081   aagcagcaaa aggaacccct ctcccatcgc ttcaacgagt tcatgacctc           caaacccaaa               1141   atccactgct tcaggagcct aaagcgtggg ctttctctca agctgggtgc           aacaccggag               1201   gatttcagca acctcccacc tgaacaaaga aggaaaaagc tgcagcagaa           agtcgatgag               1261   ttaaataaag aaattcagaa ggagatggat caaagagatg ccataacaaa           aatgaaagat               1321   gtctacctaa agaatcctca gatgggagac ccagccagtt tggatcacaa           attagcagaa               1381   gtcagccaaa atatagagaa actgcgagta gagacccaga aatttgaggc           ctggctggct               1441   gaggttgaag gccggctccc agcacgcagc gagcaggcgc gccggcagag           cggactgtac               1501   gacagccaga acccacccac agtcaacaac tgcgcccagg accgtgagag           cccagatggc               1561   agttacacag aggagcagag tcaggagagt gagatgaagg tgctggccac           ggattttgac               1621   gacgagtttg atgatgagga gcccctccct gccataggga cgtgcaaagc           tctctacaca               1681   tttgaaggtc agaatgaagg aacgatttcc gtagttgaag gagaaacatt           gtatgtcata               1741   gaggaagaca aaggcgatgg ctggacccgc attcggagaa atgaagatga           agagggttat               1801   gtccccactt catatgtcga agtctgtttg gacaaaaatg ccaaagattc           ctag            
FNBP1 Protein ( Homo sapiens )
 
         [0000]                                      SEQ ID NO: 30                1   mswgtelwdq fdnlekhtqw gidilekyik fvkerteiel syakqlrnls               kkyqpkknsk               61   eeeeykytsc kafisnlnem ndyagqhevi senmasqiiv dlaryvqelk           qerksnfhdg               121   rkaqqhietc wkqlesskrr ferdckeadr aqqyfekmda dinvtkadve           karqqaqirh               181   qmaedskady ssilqkfnhe qheyyhthip nifqkiqeme errivrmges           mktyaevdrq               241   vipiigkcld givkaaesid qkndsqlvie ayksgfeppg diefedytqp           mkrtvsdnsl               301   snsrgegkpd lkfggkskgk lwpfikknkl mslltsphqp pppppasasp           savpngpqsp               361   kqqkeplshr fnefmtskpk ihcfrslkrg lslklgatpe dfsnlppeqr           rkklqqkvde               421   lnkeiqkemd qrdaitkmkd vylknpqmgd pasldhklae vsqnieklrv           etqkfeawla               481   evegrlpars eqarrqsgly dsqnpptvnn caqdrespdg syteeqsqes           emkvlatdfd               541   defddeeplp aigtckalyt fegqnegtis vvegetlyvi eedkgdgwtr           irrnedeegy               601   vptsyvevcl dknakds            
Abl1 cDNA ( Homo sapiens )
 
         [0000]                                      SEQ ID NO: 31                1   atgttggaga tctgcctgaa gctggtgggc tgcaaatcca agaaggggct               gtcctcgtcc               61   tccagctgtt atctggaaga agcccttcag cggccagtag catctgactt           tgagcctcag               121   ggtctgagtg aagccgctcg ttggaactcc aaggaaaacc ttctcgctgg           acccagtgaa               181   aatgacccca accttttcgt tgcactgtat gattttgtgg ccagtggaga           taacactcta               241   agcataacta aaggtgaaaa gctccgggtc ttaggctata atcacaatgg           ggaatggtgt               301   gaagcccaaa ccaaaaatgg ccaaggctgg gtcccaagca actacatcac           gccagtcaac               361   agtctggaga aacactcctg gtaccatggg cctgtgtccc gcaatgccgc           tgagtatctg               421   ctgagcagcg ggatcaatgg cagcttcttg gtgcgtgaga gtgagagcag           tcctggccag               481   aggtccatct cgctgagata cgaagggagg gtgtaccatt acaggatcaa           cactgcttct               541   gatggcaagc tctacgtctc ctccgagagc cgcttcaaca ccctggccga           gttggttcat               601   catcattcaa cggtggccga cgggctcatc accacgctcc attatccagc           cccaaagcgc               661   aacaagccca ctgtctatgg tgtgtccccc aactacgaca agtgggagat           ggaacgcacg               721   gacatcacca tgaagcacaa gctgggcggg ggccagtacg gggaggtgta           cgagggcgtg               781   tggaagaaat acagcctgac ggtggccgtg aagaccttga aggaggacac           catggaggtg               841   gaagagttct tgaaagaagc tgcagtcatg aaagagatca aacaccctaa           cctggtgcag               901   ctccttgggg tctgcacccg ggagcccccg ttctatatca tcactgagtt           catgacctac               961   gggaacctcc tggactacct gagggagtgc aaccggcagg aggtgaacgc           cgtggtgctg               1021   ctgtacatgg ccactcagat ctcgtcagcc atggagtacc tggagaagaa           aaacttcatc               1081   cacagagatc ttgctgcccg aaactgcctg gtaggggaga accacttggt           gaaggtagct               1141   gattttggcc tgagcaggtt gatgacaggg gacacctaca cagcccatgc           tggagccaag               1201   ttccccatca aatggactgc acccgagagc ctggcctaca acaagttctc           catcaagtcc               1261   gacgtctggg catttggagt attgctttgg gaaattgcta cctatggcat           gtccccttac               1321   ccgggaattg acctgtccca ggtgtatgag ctgctagaga aggactaccg           catggagcgc               1381   ccagaaggct gcccagagaa ggtctatgaa ctcatgcgag catgttggca           gtggaatccc               1441   tctgaccggc cctcctttgc tgaaatccac caagcctttg aaacaatgtt           ccaggaatcc               1501   agtatctcag acgaagtgga aaaggagctg gggaaacaag gcgtccgtgg           ggctgtgagt               1561   accttgctgc aggccccaga gctgcccacc aagacgagga cctccaggag           agctgcagag               1621   cacagagaca ccactgacgt gcctgagatg cctcactcca agggccaggg           agagagcgat               1681   cctctggacc atgagcctgc cgtgtctcca ttgctccctc gaaaagagcg           aggtcccccg               1741   gagggcggcc tgaatgaaga tgagcgcctt ctccccaaag acaaaaagac           caacttgttc               1801   agcgccttga tcaagaagaa gaagaagaca gccccaaccc ctcccaaacg           cagcagctcc               1861   ttccgggaga tggacggcca gccggagcgc agaggggccg gcgaggaaga           gggccgagac               1921   atcagcaacg gggcactggc tttcaccccc ttggacacag ctgacccagc           caagtcccca               1981   aagcccagca atggggctgg ggtccccaat ggagccctcc gggagtccgg           gggctcaggc               2041   ttccggtctc cccacctgtg gaagaagtcc agcacgctga ccagcagccg           cctagccacc               2101   ggcgaggagg agggcggtgg cagctccagc aagcgcttcc tgcgctcttg           ctccgcctcc               2161   tgcgttcccc atggggccaa ggacacggag tggaggtcag tcacgctgcc           tcgggacttg               2221   cagtccacgg gaagacagtt tgactcgtcc acatttggag ggcacaaaag           tgagaagccg               2281   gctctgcctc ggaagagggc aggggagaac aggtctgacc aggtgacccg           aggcacagta               2341   acgcctcccc ccaggctggt gaaaaagaat gaggaagctg ctgatgaggt           cttcaaagac               2401   atcatggagt ccagcccggg ctccagcccg cccaacctga ctccaaaacc           cctccggcgg               2461   caggtcaccg tggcccctgc ctcgggcctc ccccacaagg aagaagctgg           aaagggcagt               2521   gccttaggga cccctgctgc agctgagcca gtgaccccca ccagcaaagc           aggctcaggt               2581   gcaccagggg gcaccagcaa gggccccgcc gaggagtcca gagtgaggag           gcacaagcac               2641   tcctctgagt cgccagggag ggacaagggg aaattgtcca ggctcaaacc           tgccccgccg               2701   cccccaccag cagcctctgc agggaaggct ggaggaaagc cctcgcagag           cccgagccag               2761   gaggcggccg gggaggcagt cctgggcgca aagacaaaag ccacgagtct           ggttgatgct               2821   gtgaacagtg acgctgccaa gcccagccag ccgggagagg gcctcaaaaa           gcccgtgctc               2881   ccggccactc caaagccaca gtccgccaag ccgtcgggga cccccatcag           cccagccccc               2941   gttccctcca cgttgccatc agcatcctcg gccctggcag gggaccagcc           gtcttccacc               3001   gccttcatcc ctctcatatc aacccgagtg tctcttcgga aaacccgcca           gcctccagag               3061   cggatcgcca gcggcgccat caccaagggc gtggtcctgg acagcaccga           ggcgctgtgc               3121   ctcgccatct ctaggaactc cgagcagatg gccagccaca gcgcagtgct           ggaggccggc               3181   aaaaacctct acacgttctg cgtgagctat gtggattcca tccagcaaat           gaggaacaag               3241   tttgccttcc gagaggccat caacaaactg gagaataatc tccgggagct           tcagatctgc               3301   ccggcgacag caggcagtgg tccagcggcc actcaggact tcagcaagct           cctcagttcg               3361   gtgaaggaaa tcagtgacat agtgcagagg tag            
ABL1 Protein ( Homo sapiens )
 
         [0000]                                      SEQ ID NO: 32                1   mleiclklvg ckskkglsss sscyleealq rpvasdfepq glseaarwns               kenllagpse               61   ndpnlfvaly dfvasgdntl sitkgeklrv lgynhngewc eaqtkngqgw           vpsnyitpvn               121   slekhswyhg pvsrnaaeyl lssgingsfl vresesspgq rsislryegr           vyhyrintas               181   dgklyvsses rfntlaelvh hhstvadgli ttlhypapkr nkptvygvsp           nydkwemert               241   ditmkhklgg gqygevyegv wkkysltvav ktlkedtmev eeflkeaavm           keikhpnlvq               301   llgvctrepp fyiitefmty gnlldylrec nrqevnavvl lymatqissa           meylekknfi               361   hrdlaarncl vgenhlvkva dfglsrlmtg dtytahagak fpikwtapes           laynkfsiks               421   dvwafgvllw eiatygmspy pgidlsqvye llekdyrmer pegcpekvye           lmracwqwnp               481   sdrpsfaeih qafetmfqes sisdevekel gkqgvrgavs tllqapelpt           ktrtsrraae               541   hrdttdvpem phskgqgesd pldhepavsp llprkergpp egglnederl           lpkdkktnlf               601   salikkkkkt aptppkrsss fremdgqper rgageeegrd isngalaftp           ldtadpaksp               661   kpsngagvpn galresggsg frsphlwkks stltssrlat geeegggsss           krflrscsas               721   cvphgakdte wrsvtlprdl qstgrqfdss tfgghksekp alprkragen           rsdqvtrgtv               781   tppprlvkkn eeaadevfkd imesspgssp pnltpkplrr qvtvapasgl           phkeeagkgs               841   algtpaaaep vtptskagsg apggtskgpa eesrvrrhkh ssespgrdkg           klsrlkpapp               901   pppaasagka ggkpsqspsq eaageavlga ktkatslvda vnsdaakpsq           pgeglkkpvl               961   patpkpqsak psgtpispap vpstlpsass alagdqpsst afiplistrv           slrktrqppe               1021   riasgaitkg vvldstealc laisrnseqm ashsavleag knlytfcvsy           vdsiqqmrnk               1081   fafreainkl ennlrelqic patagsgpaa tqdfskllss vkeisdivqr            
Nup214 cDNA ( Homo sapiens )
 
         [0000]                                      SEQ ID NO: 33                1   atgggagacg agatggatgc catgattccc gagcgggaga tgaaggattt               tcagtttaga               61   gcgctaaaga aggtgagaat ctttgactcc cctgaggaat tgcccaagga           acgctcgagt               121   ctgcttgctg tgtccaacaa atatggtctg gtcttcgctg gtggagccag           tggcttgcag               181   atttttccta ctaaaaatct tcttattcaa aataaacccg gagatgatcc           caacaaaata               241   gttgataaag tccaaggctt gctagttcct atgaaattcc caatccatca           cctggccttg               301   agctgtgata acctcacact ctctgcgtgc atgatgtcca gtgaatatgg           ttccattatt               361   gctttttttg atgttcgcac attctcaaat gaggctaaac agcaaaaacg           cccatttgcc               421   tatcataagc ttttgaaaga tgcaggaggc atggtgattg atatgaagtg           gaaccccact               481   gtcccctcca tggtggcagt ttgtctggct gatggtagta ttgctgtcct           gcaagtcacg               541   gaaacagtga aagtatgtgc aactcttcct tccacggtag cagtaacctc           tgtgtgctgg               601   agccccaaag gaaagcagct ggcagtggga aaacagaatg gaactgtggt           ccagtatctt               661   cctactttgc aggaaaaaaa agtcattcct tgtcctccgt tttatgagtc           agatcatcct               721   gtcagagttc tggatgtgct gtggattggt acctacgtct tcgccatagt           gtatgctgct               781   gcagatggga ccctggaaac gtctccagat gtggtgatgg ctctactacc           gaaaaaagaa               841   gaaaagcacc cagagatatt tgtgaacttt atggagccct gttatggcag           ctgcacggag               901   agacagcatc attactacct cagttacatt gaggaatggg atttagtgct           ggcagcatct               961   gcggcttcaa cagaagttag tatccttgct cgacaaagtg atcagattaa           ttgggaatct               1021   tggctactgg aggattctag tcgagctgaa ttgcctgtga cagacaagag           tgatgactcc               1081   ttgcccatgg gagttgtcgt agactataca aaccaagtgg aaatcaccat           cagtgatgaa               1141   aagactcttc ctcctgctcc agttctcatg ttactttcaa cagatggtgt           gctttgtcca               1201   ttttatatga ttaatcaaaa tcctggggtt aagtctctca tcaaaacacc           agagcgactt               1261   tcattagaag gagagcgaca gcccaagtca ccaggaagta ctcccactac           cccaacctcc               1321   tctcaagccc cacagaaact ggatgcttct gcagctgcag cccctgcctc           tctgccacct               1381   tcatcacctg ctgctcccat tgccactttt tctttgcttc ctgctggtgg           agcccccact               1441   gtgttctcct ttggttcttc atctttgaag tcatctgcta cggtcactgg           ggagccccct               1501   tcatattcca gtggctccga cagctccaaa gcagccccag gccctggccc           atcaaccttc               1561   tcttttgttc ccccttctaa agcctcccta gcccccaccc ctgcagcgtc           tcctgtggct               1621   ccatcagctg cttcattctc ctttggatca tctggtttta agcctaccct           ggaaagcaca               1681   ccagtgccaa gtgtgtctgc tccaaatata gcaatgaagc cctccttccc           accctcaacc               1741   tctgctgtca aagtcaacct tagtgaaaag tttactgctg cagctacctc           tactcctgtt               1801   agtagctccc agagcgcacc cccgatgtcg ccattctctt ctgcctccaa           gccagctgct               1861   tctggaccac tcagccaccc cacacctctc tcagcaccac ctagttccgt           gccattgaag               1921   tcctcagtct tgccctcacc atcaggacga tctgctcagg gcagttcaag           cccagtgccc               1981   tcaatggtac agaaatcacc caggataacc cctccagcgg caaagccagg           ctctccccag               2041   gcaaagtcac ttcagcctgc tgttgcagaa aagcagggac atcagtggaa           agattcagat               2101   cctgtaatgg ctggaattgg ggaggagatt gcacactttc agaaggagtt           ggaagagtta               2161   aaagcccgaa cttccaaagc ctgtttccaa gtgggcactt ctgaggagat           gaagatgctg               2221   cgaacagaat cagatgactt gcataccttt cttttggaga ttaaagagac           cacagagtcg               2281   cttcatggag atataagtag cctgaaaaca actttacttg agggctttgc           tggtgttgag               2341   gaagccagag aacaaaatga aagaaatcgt gactctggtt atctgcattt           gctttataaa               2401   agaccactgg atcccaagag tgaagctcag cttcaggaaa ttcggcgcct           tcatcagtat               2461   gtgaaatttg ctgtccaaga tgtgaatgat gttctagact tggagtggga           tcagcatctg               2521   gaacaaaaga aaaaacaaag gcacctgctt gtgccagagc gagagacact           gtttaacacc               2581   ctagccaaca atcgggaaat catcaaccaa cagaggaaga ggctgaatca           cctggtggat               2641   agtcttcagc agctccgcct ttacaaacag acttccctgt ggagcctgtc           ctcggctgtt               2701   ccttcccaga gcagcattca cagttttgac agtgacctgg aaagcctgtg           caatgctttg               2761   ttgaaaacca ccatagaatc tcacaccaaa tccttgccca aagtaccagc           caaactgtcc               2821   cccatgaaac aggcacaact gagaaacttc ttggccaaga ggaagacccc           accagtgaga               2881   tccactgctc cagccagcct gtctcgatca gcctttctgt ctcagagata           ttatgaagac               2941   ttggatgaag tcagctcaac gtcatctgtc tcccagtctc tggagagtga           agatgcacgg               3001   acgtcctgta aagatgacga ggcagtggtt caggcccctc ggcacgcccc           cgtggttcgc               3061   actccttcca tccagcccag tctcttgccc catgcagcac cttttgctaa           atctcacctg               3121   gttcatggtt cttcacctgg tgtgatggga acttcagtgg ctacatctgc           tagcaaaatt               3181   attcctcaag gggccgatag cacaatgctt gccacgaaaa ccgtgaaaca           tggtgcacct               3241   agtccttccc accccatctc agccccgcag gcagctgccg cagcagcact           caggcggcag               3301   atggccagtc aggcaccagc tgtaaacact ttgactgaat caacgttgaa           gaatgtccct               3361   caagtggtaa atgtgcagga attgaagaat aaccctgcaa ccccttctac           agccatgggt               3421   tcttcagtgc cctactccac agccaaaaca cctcacccag tgttgacccc           agtggctgct               3481   aaccaagcca agcaggggtc tctaataaat tcccttaagc catctgggcc           tacaccagca               3541   tccggtcagt tatcatctgg tgacaaagct tcagggacag ccaagataga           aacagctgtg               3601   acttcaaccc catctgcttc tgggcagttc agcaagcctt tctcattttc           tccatcaggg               3661   actggcttta attttgggat aatcacacca acaccgtctt ctaatttcac           tgctgcacaa               3721   ggggcaacac cctccactaa agagtcaagc cagccggacg cattctcatc           tggtggggga               3781   agcaaacctt cttatgaggc cattcctgaa agctcacctc cctcaggaat           cacatccgca               3841   tcaaacacca ccccaggaga acctgccgca tctagcagca gacctgtggc           accttctgga               3901   actgctcttt ccaccacctc tagtaagctg gaaaccccac cgtccaagct           gggagagctt               3961   ctgtttccaa gttctttggc tggagagact ctgggaagtt tttcaggact           gcgggttggc               4021   caagcagatg attctacaaa accaaccaat aaggcttcat ccacaagcct           aactagtacc               4081   cagccaacca agacgtcagg cgtgccctca gggtttaatt ttactgcccc           cccggtgtta               4141   gggaagcaca cggagccccc tgtgacatcc tctgcaacca ccacctcagt           agcaccacca               4201   gcagccacca gcacttcctc aactgccgtt tttggcagtc tgccagtcac           cagtgcagga               4261   tcctctgggg tcatcagttt tggtgggaca tctctaagtg ctggcaagac           tagtttttca               4321   tttggaagcc aacagaccaa tagcacagtg cccccatctg ccccaccacc           aactacagct               4381   gccactcccc ttccaacatc attccccaca ttgtcatttg gtagcctcct           gagttcagca               4441   actaccccct ccctgcctat gtccgctggc agaagcacag aagaggccac           ttcatcagct               4501   ttgcctgaga agccaggtga cagtgaggtc tcagcatcag cagcctcact           tctagaggag               4561   caacagtcag cccagcttcc ccaggctcct ccgcaaactt ctgactctgt           taaaaaagaa               4621   cctgttcttg cccagcctgc agtcagcaac tctggcactg cagcatctag           tactagtctt               4681   gtagcacttt ctgcagaggc taccccagcc accacggggg tccctgatgc           caggacggag               4741   gcagtaccac ctgcttcctc cttttctgtg cctgggcaga ctgctgtcac           agcagctgct               4801   atctcaagtg caggccctgt ggccgtcgaa acatcaagta cccccatagc           ctccagcacc               4861   acgtccattg ttgctcccgg cccatctgca gaggcagcag catttggtac           cgtcacttct               4921   ggctcatccg tctttgctca gcctcctgct gccagttcta gctcagcttt           caaccagctc               4981   accaacaaca cagccactgc cccctctgcc acgcccgtgt ttgggcaagt           ggcagccagc               5041   accgcaccaa gtctgtttgg gcagcagact ggtagcacag ccagcacagc           agctgccaca               5101   ccacaggtca gcagctcagg gtttagcagc ccagcttttg gtaccacagc           cccaggggtc               5161   tttggacaga caaccttcgg gcaggcctca gtctttgggc agtcggcgag           cagtgctgca               5221   agtgtctttt ccttcagtca gcctgggttc agttccgtgc ctgccttcgg           tcagcctgct               5281   tcctccactc ccacatccac cagtggaagt gtctttggtg ccgcctcaag           taccagtagc               5341   tccagttcct tctcatttgg acagtcttct cccaacacag gaggggggct           gtttggccaa               5401   agcaacgctc ctgcttttgg gcagagtcct ggctttggac agggaggctc           tgtctttggt               5461   ggtacctcag ctgccaccac aacagcagca acctctgggt tcagcttttg           ccaagcttca               5521   ggttttgggt ctagtaatac tggttctgtg tttggtcaag cagccagtac           tggtggaata               5581   gtctttggcc agcaatcatc ctcttccagt ggtagcgtgt ttgggtctgg           aaacactgga               5641   agagggggag gtttcttcag tggccttgga ggaaaaccca gtcaggatgc           agccaacaaa               5701   aacccattca gctcggccag tgggggcttt ggatccacag ctacctcaaa           tacctctaac               5761   ctatttggaa acagtggggc caagacattt ggtggatttg ccagctcgtc           gtttggagag               5821   cagaaaccca ctggcacttt cagctctgga ggaggaagtg tggcatccca           aggctttggg               5881   ttttcctctc caaacaaaac aggtggcttc ggtgctgctc cagtgtttgg           cagccctcct               5941   acttttgggg gatcccctgg gtttggaggg gtgccagcat tcggttcagc           cccagccttt               6001   acaagccctc tgggctcgac gggaggcaaa gtgttcggag agggcactgc           agctgccagc               6061   gcaggaggat tcgggtttgg gagcagcagc aacaccacat ccttcggcac           gctcgcgagt               6121   cagaatgccc ccactttcgg atcactgtcc caacagactt ctggttttgg           gacccagagt               6181   agcggattct ctggttttgg atcaggcaca ggagggttca gctttgggtc           aaataactcg               6241   tctgtccagg gttttggtgg ctggcgaagc tga            
NUP214 Protein ( Homo sapiens )
 
         [0000]                                      SEQ ID NO: 34                1   mgdemdamip eremkdfqfr alkkvrifds peelpkerss llavsnkygl               vfaggasglq               61   ifptknlliq nkpgddpnki vdkvqgllvp mkfpihhlal scdnltlsac           mmsseygsii               121   affdvrtfsn eakqqkrpfa yhkllkdagg mvidmkwnpt vpsmvavcla           dgsiavlqvt               181   etvkvcatlp stvavtsvcw spkgkqlavg kqngtvvqyl ptlqekkvip           cppfyesdhp               241   vrvldvlwig tyvfaivyaa adgtletspd vvmallpkke ekhpeifvnf           mepcygscte               301   rqhhyylsyi eewdlvlaas aastevsila rqsdqinwes wlledssrae           lpvtdksdds               361   lpmgvvvdyt nqveitisde ktlppapvlm llstdgvlcp fyminqnpgv           ksliktperl               421   slegerqpks pgstpttpts sqapqkldas aaaapaslpp sspaapiatf           sllpaggapt               481   vfsfgssslk ssatvtgepp syssgsdssk aapgpgpstf sfvppskasl           aptpaaspva               541   psaasfsfgs sgfkptlest pvpsvsapni amkpsfppst savkvnlsek           ftaaatstpv               601   sssqsappms pfssaskpaa sgplshptpl sappssvplk ssvlpspsgr           saqgssspvp               661   smvqksprit ppaakpgspq akslqpavae kqghqwkdsd pvmagigeei           ahfqkeleel               721   kartskacfq vgtseemkml rtesddlhtf lleikettes lhgdisslkt           tllegfagve               781   eareqnernr dsgylhllyk rpldpkseaq lqeirrlhqy vkfavqdvnd           vldlewdqhl               841   eqkkkqrhll vperetlfnt lannreiinq qrkrlnhlvd slqqlrlykq           tslwslssav               901   psqssihsfd sdleslcnal lkttieshtk slpkvpakls pmkqaqlrnf           lakrktppvr               961   stapaslsrs aflsqryyed ldevsstssv sqslesedar tsckddeavv           qaprhapvvr               1021   tpsiqpsllp haapfakshl vhgsspgvmg tsvatsaski ipqgadstml           atktvkhgap               1081   spshpisapq aaaaaalrrq masqapavnt ltestlknvp qvvnvqelkn           npatpstamg               1141   ssvpystakt phpvltpvaa nqakqgslin slkpsgptpa sgqlssgdka           sgtakietav               1201   tstpsasgqf skpfsfspsg tgfnfgiitp tpssnftaaq gatpstkess           qpdafssggg               1261   skpsyeaipe ssppsgitsa snttpgepaa sssrpvapsg talsttsskl           etppsklgel               1321   lfpsslaget lgsfsglrvg qaddstkptn kasstsltst qptktsgvps           gfnftappvl               1381   gkhteppvts satttsvapp aatstsstav fgslpvtsag ssgvisfggt           slsagktsfs               1441   fgsqqtnstv ppsappptta atplptsfpt lsfgsllssa ttpslpmsag           rsteeatssa               1501   lpekpgdsev sasaasllee qqsaqlpqap pqtsdsvkke pvlaqpavsn           sgtaasstsl               1561   valsaeatpa ttgvpdarte avppassfsv pgqtavtaaa issagpvave           tsstpiasst               1621   tsivapgpsa eaaafgtvts gssvfaqppa assssafnql tnntatapsa           tpvfgqvaas               1681   tapslfgqqt gstastaaat pqvsssgfss pafgttapgv fgqttfgqas           vfgqsassaa               1741   svfsfsqpgf ssvpafgqpa sstptstsgs vfgaasstss sssfsfgqss           pntggglfgq               1801   snapafgqsp gfgqggsvfg gtsaatttaa tsgfsfcqas gfgssntgsv           fgqaastggi               1861   vfgqqsssss gsvfgsgntg rgggffsglg gkpsqdaank npfssasggf           gstatsntsn               1921   lfgnsgaktf ggfasssfge qkptgtfssg ggsvasqgfg fsspnktggf           gaapvfgspp               1981   tfggspgfgg vpafgsapaf tsplgstggk vfgegtaaas aggfgfgsss           nttsfgtlas               2041   qnaptfgsls qqtsgfgtqs sgfsgfgsgt ggfsfgsnns svqgfggwrs            
Trp53 cDNA ( Homo sapiens )
 
         [0000]                                      SEQ ID NO: 35                1   atggaggagc cgcagtcaga tcctagcgtc gagccccctc tgagtcagga               aacattttca               61   gacctatgga aactacttcc tgaaaacaac gttctgtccc ccttgccgtc           ccaagcaatg               121   gatgatttga tgctgtcccc ggacgatatt gaacaatggt tcactgaaga           cccaggtcca               181   gatgaagctc ccagaatgcc agaggctgct ccccccgtgg cccctgcacc           agcagctcct               241   acaccggcgg cccctgcacc agccccctcc tggcccctgt catcttctgt           cccttcccag               301   aaaacctacc agggcagcta cggtttccgt ctgggcttct tgcattctgg           gacagccaag               361   tctgtgactt gcacgtactc ccctgccctc aacaagatgt tttgccaact           ggccaagacc               421   tgccctgtgc agctgtgggt tgattccaca cccccgcccg gcacccgcgt           ccgcgccatg               481   gccatctaca agcagtcaca gcacatgacg gaggttgtga ggcgctgccc           ccaccatgag               541   cgctgctcag atagcgatgg tctggcccct cctcagcatc ttatccgagt           ggaaggaaat               601   ttgcgtgtgg agtatttgga tgacagaaac acttttcgac atagtgtggt           ggtgccctat               661   gagccgcctg aggttggctc tgactgtacc accatccact acaactacat           gtgtaacagt               721   tcctgcatgg gcggcatgaa ccggaggccc atcctcacca tcatcacact           ggaagactcc               781   agtggtaatc tactgggacg gaacagcttt gaggtgcgtg tttgtgcctg           tcctgggaga               841   gaccggcgca cagaggaaga gaatctccgc aagaaagggg agcctcacca           cgagctgccc               901   ccagggagca ctaagcgagc actgcccaac aacaccagct cctctcccca           gccaaagaag               961   aaaccactgg atggagaata tttcaccctt cagatccgtg ggcgtgagcg           cttcgagatg               1021   ttccgagagc tgaatgaggc cttggaactc aaggatgccc aggctgggaa           ggagccaggg               1081   gggagcaggg ctcactccag ccacctgaag tccaaaaagg gtcagtctac           ctcccgccat               1141   aaaaaactca tgttcaagac agaagggcct gactcagact ga            
TRP53 Protein ( Homo sapiens )
 
         [0000]                                      SEQ ID NO: 36                1   meepqsdpsv epplsqetfs dlwkllpenn vlsplpsqam ddlmlspddi               eqwftedpgp               61   deaprmpeaa ppvapapaap tpaapapaps wplsssvpsq ktyqgsygfr           lgflhsgtak               121   svtctyspal nkmfcqlakt cpvqlwvdst pppgtrvram aiykqsqhmt           evvrrcphhe               181   rcsdsdglap pqhlirvegn lrveylddrn tfrhsvvvpy eppevgsdct           tihynymcns               241   scmggmnrrp iltiitleds sgnllgrnsf evrvcacpgr drrteeenlr           kkgephhelp               301   pgstkralpn ntssspqpkk kpldgeyftl qirgrerfem frelnealel           kdaqagkepg               361   gsrahsshlk skkgqstsrh kklmfktegp dsd            
Bcl6 cDNA ( Homo sapiens )
 
         [0000]                                      SEQ ID NO: 37                1   atggcctcgc cggctgacag ctgtatccag ttcacccgcc atgccagtga               tgttcttctc               61   aaccttaatc gtctccggag tcgagacatc ttgactgatg ttgtcattgt           tgtgagccgt               121   gagcagttta gagcccataa aacggtcctc atggcctgca gtggcctgtt           ctatagcatc               181   tttacagacc agttgaaatg caaccttagt gtgatcaatc tagatcctga           gatcaaccct               241   gagggattct gcatcctcct ggacttcatg tacacatctc ggctcaattt           gcgggagggc               301   aacatcatgg ctgtgatggc cacggctatg tacctgcaga tggagcatgt           tgtggacact               361   tgccggaagt ttattaaggc cagtgaagca gagatggttt ctgccatcaa           gcctcctcgt               421   gaagagttcc tcaacagccg gatgctgatg ccccaagaca tcatggccta           tcggggtcgt               481   gaggtggtgg agaacaacct gccactgagg agcgcccctg ggtgtgagag           cagagccttt               541   gcccccagcc tgtacagtgg cctgtccaca ccgccagcct cttattccat           gtacagccac               601   ctccctgtca gcagcctcct cttctccgat gaggagtttc gggatgtccg           gatgcctgtg               661   gccaacccct tccccaagga gcgggcactc ccatgtgata gtgccaggcc           agtccctggt               721   gagtacagcc ggccgacttt ggaggtgtcc cccaatgtgt gccacagcaa           tatctattca               781   cccaaggaaa caatcccaga agaggcacga agtgatatgc actacagtgt           ggctgagggc               841   ctcaaacctg ctgccccctc agcccgaaat gccccctact tcccttgtga           caaggccagc               901   aaagaagaag agagaccctc ctcggaagat gagattgccc tgcatttcga           gccccccaat               961   gcacccctga accggaaggg tctggttagt ccacagagcc cccagaaatc           tgactgccag               1021   cccaactcgc ccacagagtc ctgcagcagt aagaatgcct gcatcctcca           ggcttctggc               1081   tcccctccag ccaagagccc cactgacccc aaagcctgca actggaagaa           atacaagttc               1141   atcgtgctca acagcctcaa ccagaatgcc aaaccagagg ggcctgagca           ggctgagctg               1201   ggccgccttt ccccacgagc ctacacggcc ccacctgcct gccagccacc           catggagcct               1261   gagaaccttg acctccagtc cccaaccaag ctgagtgcca gcggggagga           ctccaccatc               1321   ccacaagcca gccggctcaa taacatcgtt aacaggtcca tgacgggctc           tccccgcagc               1381   agcagcgaga gccactcacc actctacatg caccccccga agtgcacgtc           ctgcggctct               1441   cagtccccac agcatgcaga gatgtgcctc cacaccgctg gccccacgtt           ccctgaggag               1501   atgggagaga cccagtctga gtactcagat tctagctgtg agaacggggc           cttcttctgc               1561   aatgagtgtg actgccgctt ctctgaggag gcctcactca agaggcacac           gctgcagacc               1621   cacagtgaca aaccctacaa gtgtgaccgc tgccaggcct ccttccgcta           caagggcaac               1681   ctcgccagcc acaagaccgt ccataccggt gagaaaccct atcgttgcaa           catctgtggg               1741   gcccagttca accggccagc caacctgaaa acccacactc gaattcactc           tggagagaag               1801   ccctacaaat gcgaaacctg cggagccaga tttgtacagg tggcccacct           ccgtgcccat               1861   gtgcttatcc acactggtga gaagccctat ccctgtgaaa tctgtggcac           ccgtttccgg               1921   caccttcaga ctctgaagag ccacctgcga atccacacag gagagaaacc           ttaccattgt               1981   gagaagtgta acctgcattt ccgtcacaaa agccagctgc gacttcactt           gcgccagaag               2041   catggcgcca tcaccaacac caaggtgcaa taccgcgtgt cagccactga           cctgcctccg               2101   gagctcccca aagcctgctg a            
BCL6 Protein ( Homo sapiens )
 
         [0000]                                      SEQ ID NO: 38                1   maspadsciq ftrhasdvll nlnrlrsrdi ltdvvivvsr eqfrahktvl               macsglfysi               61   ftdqlkcnls vinldpeinp egfcilldfm ytsrlnlreg nimavmatam           ylqmehvvdt               121   crkfikasea emvsaikppr eeflnsrmlm pqdimayrgr evvennlplr           sapgcesraf               181   apslysglst ppasysmysh lpvssllfsd eefrdvrmpv anpfpkeral           pcdsarpvpg               241   eysrptlevs pnvchsniys pketipeear sdmhysvaeg lkpaapsarn           apyfpcdkas               301   keeerpssed eialhfeppn aplnrkglvs pqspqksdcq pnsptescss           knacilqasg               361   sppaksptdp kacnwkkykf ivlnslnqna kpegpeqael grlsprayta           ppacqppmep               421   enldlqsptk lsasgedsti pqasrlnniv nrsmtgsprs sseshsplym           hppkctscgs               481   qspqhaemcl htagptfpee mgetqseysd sscengaffc necdcrfsee           aslkrhtlqt               541   hsdkpykcdr cqasfrykgn lashktvhtg ekpyrcnicg aqfnrpanlk           thtrihsgek               601   pykcetcgar fvqvahlrah vlihtgekpy pceicgtrfr hlqtlkshlr           ihtgekpyhc               661   ekcnlhfrhk sqlrlhlrqk hgaitntkvq yrvsatdlpp elpkac            
Negr1 cDNA ( Homo sapiens )
 
         [0000]                                      SEQ ID NO: 39                1   atggacatga tgctgttggt gcagggtgct tgttgctcga accagtggct               ggcggcggtg               61   ctcctcagcc tgtgctgcct gctaccctcc tgcctcccgg ctggacagag           tgtggacttc               121   ccctgggcgg ccgtggacaa catgatggtc agaaaagggg acacggcggt           gcttaggtgt               181   tatttggaag atggagcttc aaagggtgcc tggctgaacc ggtcaagtat           tatttttgcg               241   ggaggtgata agtggtcagt ggatcctcga gtttcaattt caacattgaa           taaaagggac               301   tacagcctcc agatacagaa tgtagatgtg acagatgatg gcccatacac           gtgttctgtt               361   cagactcaac atacacccag aacaatgcag gtgcatctaa ctgtgcaagt           tcctcctaag               421   atatatgaca tctcaaatga tatgaccgtc aatgaaggaa ccaacgtcac           tcttacttgt               481   ttggccactg ggaaaccaga gccttccatt tcttggcgac acatctcccc           atcagcaaaa               541   ccatttgaaa atggacaata tttggacatt tatggaatta caagggacca           ggctggggaa               601   tatgaatgca gtgcggaaaa tgatgtgtca ttcccagatg tgaggaaagt           aaaagttgtt               661   gtcaactttg ctcctactat tcaggaaatt aaatctggca ccgtgacccc           cggacgcagt               721   ggcctgataa gatgtgaagg tgcaggtgtg ccgcctccag cctttgaatg           gtacaaagga               781   gagaagaagc tcttcaatgg ccaacaagga attattattc aaaattttag           cacaagatcc               841   attctcactg ttaccaacgt gacacaggag cacttcggca attatacctg           tgtggctgcc               901   aacaagctag gcacaaccaa tgcgagcctg cctcttaacc ctccaagtac           agcccagtat               961   ggaattaccg ggagcgctga tgttcttttc tcctgctggt accttgtgtt           gacactgtcc               1021   tctttcacca gcatattcta cctgaagaat gccattctac aataa            
NEGR1 Protein ( Homo sapiens )
 
         [0000]                              SEQ ID NO: 40            1   mdmmllvqga ccsnqwlaav llslccllps clpagqsvdf           pwaavdnmmv rkgdtavlrc               61   yledgaskga wlnrssiifa ggdkwsvdpr vsistlnkrd           yslqiqnvdv tddgpytcsv               121   qtqhtprtmq vhltvqvppk iydisndmtv negtnvtltc           latgkpepsi swrhispsak               181   pfengqyldi ygitrdqage yecsaendvs fpdvrkvkvv           vnfaptiqei ksgtvtpgrs               241   glircegagv pppafewykg ekklfngqqg iiiqnfstrs           iltvtnvtqe hfgnytcvaa               301   nklgttnasl plnppstaqy gitgsadvlf scwylvltls           sftsifylkn ailq            
Baalc cDNA ( Homo sapiens )
 
         [0000]                              SEQ ID NO: 41            1   atgggctgcg gcgggagccg ggcggatgcc atcgagcccc           gctactacga gagctggacc               61   cgggagacag aatccacctg gctcacctac accgactcgg           acgcgccgcc cagcgccgcc               121   gccccggaca gcggccccga agcgggcggc ctgcactcgg           gcatgctgga agatggactg               181   ccctccaatg gtgtgccccg atctacagcc ccaggtggaa           tacccaaccc agagaagaag               241   acgaactgtg agacccagtg cccaaatccc cagagcctca           gctcaggccc tctgacccag               301   aaacagaatg gccttcagac cacagaggct aaaagagatg           ctaagagaat gcctgcaaaa               361   gaagtcacca ttaatgtaac agatagcatc caacagatgg           acagaagtcg aagaatcaca               421   aagaactgtg tcaactag            
BAALC Protein ( Homo sapiens )
 
         [0000]                              SEQ ID NO: 42            1   mgcggsrada iepryyeswt retestwlty tdsdappsaa           apdsgpeagg lhsgmledgl               61   psngvprsta pggipnpekk tncetqcpnp qslssgpltq           kqnglqttea krdakrmpak               121   evtinvtdsi qqmdrsrrit kncvn            
Fzd6 cDNA ( Homo sapiens )
 
         [0000]                                      SEQ ID NO: 43                1   atggaaatgt ttacattttt gttgacgtgt atttttctac ccctcctaag               agggcacagt               61   ctcttcacct gtgaaccaat tactgttccc agatgtatga aaatggccta           caacatgacg               121   tttttcccta atctgatggg tcattatgac cagagtattg ccgcggtgga           aatggagcat               181   tttcttcctc tcgcaaatct ggaatgttca ccaaacattg aaactttcct           ctgcaaagca               241   tttgtaccaa cctgcataga acaaattcat gtggttccac cttgtcgtaa           actttgtgag               301   aaagtatatt ctgattgcaa aaaattaatt gacacttttg ggatccgatg           gcctgaggag               361   cttgaatgtg acagattaca atactgtgat gagactgttc ctgtaacttt           tgatccacac               421   acagaatttc ttggtcctca gaagaaaaca gaacaagtcc aaagagacat           tggattttgg               481   tgtccaaggc atcttaagac ttctggggga caaggatata agtttctggg           aattgaccag               541   tgtgcgcctc catgccccaa catgtatttt aaaagtgatg agctagagtt           tgcaaaaagt               601   tttattggaa cagtttcaat attttgtctt tgtgcaactc tgttcacatt           ccttactttt               661   ttaattgatg ttagaagatt cagataccca gagagaccaa ttatatatta           ctctgtctgt               721   tacagcattg tatctcttat gtacttcatt ggatttttgc taggcgatag           cacagcctgc               781   aataaggcag atgagaagct agaacttggt gacactgttg tcctaggctc           tcaaaataag               841   gcttgcaccg ttttgttcat gcttttgtat tttttcacaa tggctggcac           tgtgtggtgg               901   gtgattctta ccattacttg gttcttagct gcaggaagaa aatggagttg           tgaagccatc               961   gagcaaaaag cagtgtggtt tcatgctgtt gcatggggaa caccaggttt           cctgactgtt               1021   atgcttcttg ctatgaacaa agttgaagga gacaacatta gtggagtttg           ctttgttggc               1081   ctttatgacc tggatgcttc tcgctacttt gtactcttgc cactgtgcct           ttgtgtgttt               1141   gttgggctct ctcttctttt agctggcatt atttccttaa atcatgttcg           acaagtcata               1201   caacatgatg gccggaacca agaaaaacta aagaaattta tgattcgaat           tggagtcttc               1261   agcggcttgt atcttgtgcc attagtgaca cttctcggat gttacgtcta           tgagcaagtg               1321   aacaggatta cctgggagat aacttgggtc tctgatcatt gtcgtcagta           ccatatccca               1381   tgtccttatc aggcaaaagc aaaagctcga ccagaattgg ctttatttat           gataaaatac               1441   ctgatgacat taattgttgg catctctgct gtcttctggg ttggaagcaa           aaagacatgc               1501   acagaatggg ctgggttttt taaacgaaat cgcaagagag atccaatcag           tgaaagtcga               1561   agagtactac aggaatcatg tgagtttttc ttaaagcaca attctaaagt           taaacacaaa               1621   aagaagcact ataaaccaag ttcacacaag ctgaaggtca tttccaaatc           catgggaacc               1681   agcacaggag ctacagcaaa tcatggcact tctgcagtag caattactag           ccatgattac               1741   ctaggacaag aaactttgac agaaatccaa acctcaccag aaacatcaat           gagagaggtg               1801   aaagcggacg gagctagcac ccccaggtta agagaacagg actgtggtga           acctgcctcg               1861   ccagcagcat ccatctccag actctctggg gaacaggtcg acgggaaggg           ccaggcaggc               1921   agtgtatctg aaagtgcgcg gagtgaagga aggattagtc caaagagtga           tattactgac               1981   actggcctgg cacagagcaa caatttgcag gtccccagtt cttcagaacc           aagcagcctc               2041   aaaggttcca catctctgct tgttcacccg gtttcaggag tgagaaaaga           gcagggaggt               2101   ggttgtcatt cagatacttg a            
FZD6 Protein ( Homo sapiens )
 
         [0000]                              SEQ ID NO: 44            1   memftflltc iflpllrghs lftcepitvp rcmkmaynmt           ffpnlmghyd qsiaavemeh               61   flplanlecs pnietflcka fvptcieqih vvpperklce           kvysdckkli dtfgirwpee               121   lecdrlqycd etvpvtfdph teflgpqkkt eqvqrdigfw           cprhlktsgg qgykflgidq               181   cappcpnmyf ksdelefaks figtvsifcl catlftfltf           lidvrrfryp erpiiyysvc               241   ysivslmyfi gfllgdstac nkadeklelg dtvvlgsqnk           actvlfmlly fftmagtvww               301   viltitwfla agrkwsceai eqkavwfhav awgtpgfltv           mllamnkveg dnisgvcfvg               361   lydldasryf vllplclcvf vglslllagi islnhvrqvi           qhdgrnqekl kkfmirigvf               421   sglylvplvt llgcyvyeqv nritweitwv sdhcrqyhip           cpyqakakar pelalfmiky               481   lmtlivgisa vfwvgskktc tewagffkrn rkrdpisesr           rvlqesceff lkhnskvkhk               541   kkhykpsshk lkvisksmgt stgatanhgt savaitshdy           lgqetlteiq tspetsmrev               601   kadgastprl reqdcgepas paasisrlsg eqvdgkgqag           svsesarseg rispksditd               661   tglaqsnnlq vpsssepssl kgstsllvhp vsgvrkeqgg           gchsdt            
Crebbp cDNA ( Homo sapiens )
 
         [0000]                                      SEQ ID NO: 45                1   atggctgaga acttgctgga cggaccgccc aaccccaaaa gagccaaact               cagctcgccc               61   ggtttctcgg cgaatgacag cacagatttt ggatcattgt ttgacttgga           aaatgatctt               121   cctgatgagc tgatacccaa tggaggagaa ttaggccttt taaacagtgg           gaaccttgtt               181   ccagatgctg cttccaaaca taaacaactg tcggagcttc tacgaggagg           cagcggctct               241   agtatcaacc caggaatagg aaatgtgagc gccagcagcc ccgtgcagca           gggcctgggt               301   ggccaggctc aagggcagcc gaacagtgct aacatggcca gcctcagtgc           catgggcaag               361   agccctctga gccagggaga ttcttcagcc cccagcctgc ctaaacaggc           agccagcacc               421   tctgggccca cccccgctgc ctcccaagca ctgaatccgc aagcacaaaa           gcaagtgggg               481   ctggcgacta gcagccctgc cacgtcacag actggacctg gtatctgcat           gaatgctaac               541   tttaaccaga cccacccagg cctcctcaat agtaactctg gccatagctt           aattaatcag               601   gcttcacaag ggcaggcgca agtcatgaat ggatctcttg gggctgctgg           cagaggaagg               661   ggagctggaa tgccgtaccc tactccagcc atgcagggcg cctcgagcag           cgtgctggct               721   gagaccctaa cgcaggtttc cccgcaaatg actggtcacg cgggactgaa           caccgcacag               781   gcaggaggca tggccaagat gggaataact gggaacacaa gtccatttgg           acagcccttt               841   agtcaagctg gagggcagcc aatgggagcc actggagtga acccccagtt           agccagcaaa               901   cagagcatgg tcaacagttt gcccaccttc cctacagata tcaagaatac           ttcagtcacc               961   aacgtgccaa atatgtctca gatgcaaaca tcagtgggaa ttgtacccac           acaagcaatt               1021   gcaacaggcc ccactgcaga tcctgaaaaa cgcaaactga tacagcagca           gctggttcta               1081   ctgcttcatg ctcataagtg tcagagacga gagcaagcaa acggagaggt           tcgggcctgc               1141   tcgctcccgc attgtcgaac catgaaaaac gttttgaatc acatgacgca           ttgtcaggct               1201   gggaaagcct gccaagttgc ccattgtgca tcttcacgac aaatcatctc           tcattggaag               1261   aactgcacac gacatgactg tcctgtttgc ctccctttga aaaatgccag           tgacaagcga               1321   aaccaacaaa ccatcctggg gtctccagct agtggaattc aaaacacaat           tggttctgtt               1381   ggcacagggc aacagaatgc cacttcttta agtaacccaa atcccataga           ccccagctcc               1441   atgcagcgag cctatgctgc tctcggactc ccctacatga accagcccca           gacgcagctg               1501   cagcctcagg ttcctggcca gcaaccagca cagcctcaaa cccaccagca           gatgaggact               1561   ctcaaccccc tgggaaataa tccaatgaac attccagcag gaggaataac           aacagatcag               1621   cagcccccaa acttgatttc agaatcagct cttccgactt ccctgggggc           cacaaaccca               1681   ctgatgaacg atggctccaa ctctggtaac attggaaccc tcagcactat           accaacagca               1741   gctcctcctt ctagcaccgg tgtaaggaaa ggctggcacg aacatgtcac           tcaggacctg               1801   cggagccatc tagtgcataa actcgtccaa gccatcttcc caacacctga           tcccgcagct               1861   ctaaaggatc gccgcatgga aaacctggta gcctatgcta agaaagtgga           aggggacatg               1921   tacgagtctg ccaacagcag ggatgaatat tatcacttat tagcagagaa           aatctacaag               1981   atacaaaaag aactagaaga aaaacggagg tcgcgtttac ataaacaagg           catcttgggg               2041   aaccagccag ccttaccagc cccgggggct cagccccctg tgattccaca           ggcacaacct               2101   gtgagacctc caaatggacc cctgtccctg ccagtgaatc gcatgcaagt           ttctcaaggg               2161   atgaattcat ttaaccccat gtccttgggg aacgtccagt tgccacaagc           acccatggga               2221   cctcgtgcag cctccccaat gaaccactct gtccagatga acagcatggg           ctcagtgcca               2281   gggatggcca tttctccttc ccgaatgcct cagcctccga acatgatggg           tgcacacacc               2341   aacaacatga tggcccaggc gcccgctcag agccagtttc tgccacagaa           ccagttcccg               2401   tcatccagcg gggcgatgag tgtgggcatg gggcagccgc cagcccaaac           aggcgtgtca               2461   cagggacagg tgcctggtgc tgctcttcct aaccctctca acatgctggg           gcctcaggcc               2521   agccagctac cttgccctcc agtgacacag tcaccactgc acccaacacc           gcctcctgct               2581   tccacggctg ctggcatgcc atctctccag cacacgacac cacctgggat           gactcctccc               2641   cagccagcag ctcccactca gccatcaact cctgtgtcgt cttccgggca           gactcccacc               2701   ccgactcctg gctcagtgcc cagtgctacc caaacccaga gcacccctac           agtccaggca               2761   gcagcccagg cccaggtgac cccgcagcct caaaccccag ttcagccccc           gtctgtggct               2821   acccctcagt catcgcagca acagccgacg cctgtgcacg cccagcctcc           tggcacaccg               2881   ctttcccagg cagcagccag cattgataac agagtcccta ccccctcctc           ggtggccagc               2941   gcagaaacca attcccagca gccaggacct gacgtacctg tgctggaaat           gaagacggag               3001   acccaagcag aggacactga gcccgatcct ggtgaatcca aaggggagcc           caggtctgag               3061   atgatggagg aggatttgca aggagcttcc caagttaaag aagaaacaga           catagcagag               3121   cagaaatcag aaccaatgga agtggatgaa aagaaacctg aagtgaaagt           agaagttaaa               3181   gaggaagaag agagtagcag taacggcaca gcctctcagt caacatctcc           ttcgcagccg               3241   cgcaaaaaaa tctttaaacc agaggagtta cgccaggccc tcatgccaac           cctagaagca               3301   ctgtatcgac aggacccaga gtcattacct ttccggcagc ctgtagatcc           ccagctcctc               3361   ggaattccag actattttga catcgtaaag aatcccatgg acctctccac           catcaagcgg               3421   aagctggaca cagggcaata ccaagagccc tggcagtacg tggacgacgt           ctggctcatg               3481   ttcaacaatg cctggctcta taatcgcaag acatcccgag tctataagtt           ttgcagtaag               3541   cttgcagagg tctttgagca ggaaattgac cctgtcatgc agtcccttgg           atattgctgt               3601   ggacgcaagt atgagttttc cccacagact ttgtgctgct atgggaagca           gctgtgtacc               3661   attcctcgcg atgctgccta ctacagctat cagaataggt atcatttctg           tgagaagtgt               3721   ttcacagaga tccagggcga gaatgtgacc ctgggtgacg acccttcaca           gccccagacg               3781   acaatttcaa aggatcagtt tgaaaagaag aaaaatgata ccttagaccc           cgaacctttc               3841   gttgattgca aggagtgtgg ccggaagatg catcagattt gcgttctgca           ctatgacatc               3901   atttggcctt caggttttgt gtgcgacaac tgcttgaaga aaactggcag           acctcgaaaa               3961   gaaaacaaat tcagtgctaa gaggctgcag accacaagac tgggaaacca           cttggaagac               4021   cgagtgaaca aatttttgcg gcgccagaat caccctgaag ccggggaggt           ttttgtccga               4081   gtggtggcca gctcagacaa gacggtggag gtcaagcccg ggatgaagtc           acggtttgtg               4141   gattctgggg aaatgtctga atctttccca tatcgaacca aagctctgtt           tgcttttgag               4201   gaaattgacg gcgtggatgt ctgctttttt ggaatgcacg tccaagaata           cggctctgat               4261   tgcccccctc caaacacgag gcgtgtgtac atttcttatc tggatagtat           tcatttcttc               4321   cggccacgtt gcctccgcac agccgtttac catgagatcc ttattggata           tttagagtat               4381   gtgaagaaat tagggtatgt gacagggcac atctgggcct gtcctccaag           tgaaggagat               4441   gattacatct tccattgcca cccacctgat caaaaaatac ccaagccaaa           acgactgcag               4501   gagtggtaca aaaagatgct ggacaaggcg tttgcagagc ggatcatcca           tgactacaag               4561   gatattttca aacaagcaac tgaagacagg ctcaccagtg ccaaggaact           gccctatttt               4621   gaaggtgatt tctggcccaa tgtgttagaa gagagcatta aggaactaga           acaagaagaa               4681   gaggagagga aaaaggaaga gagcactgca gccagtgaaa ccactgaggg           cagtcagggc               4741   gacagcaaga atgccaagaa gaagaacaac aagaaaacca acaagaacaa           aagcagcatc               4801   agccgcgcca acaagaagaa gcccagcatg cccaacgtgt ccaatgacct           gtcccagaag               4861   ctgtatgcca ccatggagaa gcacaaggag gtcttcttcg tgatccacct           gcacgctggg               4921   cctgtcatca acaccctgcc ccccatcgtc gaccccgacc ccctgctcag           ctgtgacctc               4981   atggatgggc gcgacgcctt cctcaccctc gccagagaca agcactggga           gttctcctcc               5041   ttgcgccgct ccaagtggtc cacgctctgc atgctggtgg agctgcacac           ccagggccag               5101   gaccgctttg tctacacctg caacgagtgc aagcaccacg tggagacgcg           ctggcactgc               5161   actgtgtgcg aggactacga cctctgcatc aactgctata acacgaagag           ccatgcccat               5221   aagatggtga agtgggggct gggcctggat gacgagggca gcagccaggg           cgagccacag               5281   tcaaagagcc cccaggagtc acgccggctg agcatccagc gctgcatcca           gtcgctggtg               5341   cacgcgtgcc agtgccgcaa cgccaactgc tcgctgccat cctgccagaa           gatgaagcgg               5401   gtggtgcagc acaccaaggg ctgcaaacgc aagaccaacg ggggctgccc           ggtgtgcaag               5461   cagctcatcg ccctctgctg ctaccacgcc aagcactgcc aagaaaacaa           atgccccgtg               5521   cccttctgcc tcaacatcaa acacaagctc cgccagcagc agatccagca           ccgcctgcag               5581   caggcccagc tcatgcgccg gcggatggcc accatgaaca cccgcaacgt           gcctcagcag               5641   agtctgcctt ctcctacctc agcaccgccc gggaccccca cacagcagcc           cagcacaccc               5701   cagacgccgc agccccctgc ccagccccaa ccctcacccg tgagcatgtc           accagctggc               5761   ttccccagcg tggcccggac tcagcccccc accacggtgt ccacagggaa           gcctaccagc               5821   caggtgccgg cccccccacc cccggcccag ccccctcctg cagcggtgga           agcggctcgg               5881   cagatcgagc gtgaggccca gcagcagcag cacctgtacc gggtgaacat           caacaacagc               5941   atgcccccag gacgcacggg catggggacc ccggggagcc agatggcccc           cgtgagcctg               6001   aatgtgcccc gacccaacca ggtgagcggg cccgtcatgc ccagcatgcc           tcccgggcag               6061   tggcagcagg cgccccttcc ccagcagcag cccatgccag gcttgcccag           gcctgtgata               6121   tccatgcagg cccaggcggc cgtggctggg ccccggatgc ccagcgtgca           gccacccagg               6181   agcatctcac ccagcgctct gcaagacctg ctgcggaccc tgaagtcgcc           cagctcccct               6241   cagcagcaac agcaggtgct gaacattctc aaatcaaacc cgcagctaat           ggcagctttc               6301   atcaaacagc gcacagccaa gtacgtggcc aatcagcccg gcatgcagcc           ccagcctggc               6361   ctccagtccc agcccggcat gcaaccccag cctggcatgc accagcagcc           cagcctgcag               6421   aacctgaatg ccatgcaggc tggcgtgccg cggcccggtg tgcctccaca           gcagcaggcg               6481   atgggaggcc tgaaccccca gggccaggcc ttgaacatca tgaacccagg           acacaacccc               6541   aacatggcga gtatgaatcc acagtaccga gaaatgttac ggaggcagct           gctgcagcag               6601   cagcagcaac agcagcagca acaacagcag caacagcagc agcagcaagg           gagtgccggc               6661   atggctgggg gcatggcggg gcacggccag ttccagcagc ctcaaggacc           cggaggctac               6721   ccaccggcca tgcagcagca gcagcgcatg cagcagcatc tccccctcca           gggcagctcc               6781   atgggccaga tggcggctca gatgggacag cttggccaga tggggcagcc           ggggctgggg               6841   gcagacagca cccccaacat ccagcaagcc ctgcagcagc ggattctgca           gcaacagcag               6901   atgaagcagc agattgggtc cccaggccag ccgaacccca tgagccccca           gcaacacatg               6961   ctctcaggac agccacaggc ctcgcatctc cctggccagc agatcgccac           gtcccttagt               7021   aaccaggtgc ggtctccagc ccctgtccag tctccacggc cccagtccca           gcctccacat               7081   tccagcccgt caccacggat acagccccag ccttcgccac accacgtctc           accccagact               7141   ggttcccccc accccggact cgcagtcacc atggccagct ccatagatca           gggacacttg               7201   gggaaccccg aacagagtgc aatgctcccc cagctgaaca cccccagcag           gagtgcgctg               7261   tccagcgaac tgtccctggt cggggacacc acgggggaca cgctagagaa           gtttgtggag               7321   ggcttgtag            
CREBBP Protein ( Homo sapiens )
 
         [0000]                                      SEQ ID NO: 46                1   maenlldgpp npkraklssp gfsandstdf gslfdlendl pdelipngge               lgllnsgnlv               61   pdaaskhkql sellrggsgs sinpgignvs asspvqqglg gqaqgqpnsa           nmaslsamgk               121   splsqgdssa pslpkqaast sgptpaasqa lnpqaqkqvg latsspatsq           tgpgicmnan               181   fnqthpglln snsghslinq asqgqaqvmn gslgaagrgr gagmpyptpa           mqgasssvla               241   etltqvspqm tghaglntaq aggmakmgit gntspfgqpf sqaggqpmga           tgvnpqlask               301   qsmvnslptf ptdikntsvt nvpnmsqmqt svgivptqai atgptadpek           rkliqqqlvl               361   llhahkcqrr eqangevrac slphcrtmkn vlnhmthcqa gkacqvahca           ssrqiishwk               421   nctrhdcpvc lplknasdkr nqqtilgspa sgiqntigsv gtgqqnatsl           snpnpidpss               481   mqrayaalgl pymnqpqtql qpqvpgqqpa qpqthqqmrt lnplgnnpmn           ipaggittdq               541   qppnlisesa lptslgatnp lmndgsnsgn igtlstipta appsstgvrk           gwhehvtqdl               601   rshlvhklvq aifptpdpaa lkdrrmenlv ayakkvegdm yesansrdey           yhllaekiyk               661   iqkeleekrr srlhkqgilg nqpalpapga qppvipqaqp vrppngplsl           pvnrmqvsqg               721   mnsfnpmslg nvqlpqapmg praaspmnhs vqmnsmgsvp gmaispsrmp           qppnmmgaht               781   nnmmaqapaq sqflpqnqfp sssgamsvgm gqppaqtgvs qgqvpgaalp           nplnmlgpqa               841   sqlpcppvtq splhptpppa staagmpslq httppgmtpp qpaaptqpst           pvsssgqtpt               901   ptpgsvpsat qtqstptvqa aaqaqvtpqp qtpvqppsva tpqssqqqpt           pvhaqppgtp               961   lsqaaasidn rvptpssvas aetnsqqpgp dvpvlemkte tqaedtepdp           geskgeprse               1021   mmeedlqgas qvkeetdiae qksepmevde kkpevkvevk eeeesssngt           asqstspsqp               1081   rkkifkpeel rqalmptlea lyrqdpeslp frqpvdpqll gipdyfdivk           npmdlstikr               1141   kldtgqyqep wqyvddvwlm fnnawlynrk tsrvykfcsk laevfeqeid           pvmqslgycc               1201   grkyefspqt lccygkqlct iprdaayysy qnryhfcekc fteiqgenvt           lgddpsqpqt               1261   tiskdqfekk kndtldpepf vdckecgrkm hqicvlhydi iwpsgfvcdn           clkktgrprk               1321   enkfsakrlq ttrlgnhled rvnkflrrqn hpeagevfvr vvassdktve           vkpgmksrfv               1381   dsgemsesfp yrtkalfafe eidgvdvcff gmhvqeygsd cpppntrrvy           isyldsihff               1441   rprclrtavy heiligyley vkklgyvtgh iwacppsegd dyifhchppd           qkipkpkrlq               1501   ewykkmldka faeriihdyk difkqatedr ltsakelpyf egdfwpnvle           esikeleqee               1561   eerkkeesta asettegsqg dsknakkknn kktnknkssi srankkkpsm           pnvsndlsqk               1621   lyatmekhke vffvihlhag pvintlppiv dpdpllscdl mdgrdafltl           ardkhwefss               1681   lrrskwstlc mlvelhtqgq drfvytcnec khhvetrwhc tvcedydlci           ncyntkshah               1741   kmvkwglgld degssqgepq skspqesrrl siqrciqslv hacqcrnanc           slpscqkmkr               1801   vvqhtkgckr ktnggcpvck qlialccyha khcqenkcpv pfclnikhkl           rqqqiqhrlq               1861   qaqlmrrrma tmntrnvpqq slpsptsapp gtptqqpstp qtpqppaqpq           pspvsmspag               1921   fpsvartqpp ttvstgkpts qvpappppaq pppaaveaar qiereaqqqq           hlyrvninns               1981   mppgrtgmgt pgsqmapvsl nvprpnqvsg pvmpsmppgq wqqaplpqqq           pmpglprpvi               2041   smqaqaavag prmpsvqppr sispsalqdl lrtlkspssp qqqqqvlnil           ksnpqlmaaf               2101   ikqrtakyva nqpgmqpqpg lqsqpgmqpq pgmhqqpslq nlnamqagvp           rpgvppqqqa               2161   mgglnpqgqa lnimnpghnp nmasmnpqyr emlrrqllqg qqqqqqqqqq           qqqqqqgsag               2221   maggmaghgq fqqpqgpggy ppamqqqqrm qqhlplqgss mgqmaaqmgq           lgqmgqpglg               2281   adstpniqqa lggrilqqqg mkgqigspgq pnpmspqqhm lsgqpgashl           pgqqiatsls               2341   nqvrspapvq sprpqsqpph sspspriqpq psphhvspqt gsphpglavt           massidqghl               2401   gnpeqsamlp qlntpsrsal sselslvgdt tgdtlekfve gl            
C2ta cDNA ( Homo sapiens )
 
         [0000]                                      SEQ ID NO: 47                1   atgcgttgcc tggctccacg ccctgctggg tcctacctgt cagagcccca               aggcagctca               61   cagtgtgcca ccatggagtt ggggccccta gaaggtggct acctggagct           tcttaacagc               121   gatgctgacc ccctgtgcct ctaccacttc tatgaccaga tggacctggc           tggagaagaa               181   gagattgagc tctactcaga acccgacaca gacaccatca actgcgacca           gttcagcagg               241   ctgttgtgtg acatggaagg tgatgaagag accagggagg cttatgccaa           tatcgcggaa               301   ctggaccagt atgtcttcca ggactcccag ctggagggcc tgagcaagga           cattttcaag               361   cacataggac cagatgaagt gatcggtgag agtatggaga tgccagcaga           agttgggcag               421   aaaagtcaga aaagaccctt cccagaggag cttccggcag acctgaagca           ctggaagcca               481   gctgagcccc ccactgtggt gactggcagt ctcctagtgg gaccagtgag           cgactgctcc               541   accctgccct gcctgccact gcctgcgctg ttcaaccagg agccagcctc           cggccagatg               601   cgcctggaga aaaccgacca gattcccatg cctttctcca gttcctcgtt           gagctgcctg               661   aatctccctg agggacccat ccagtttgtc cccaccatct ccactctgcc           ccatgggctc               721   tggcaaatct ctgaggctgg aacaggggtc tccagtatat tcatctacca           tggtgaggtg               781   ccccaggcca gccaagtacc ccctcccagt ggattcactg tccacggcct           cccaacatct               841   ccagaccggc caggctccac cagccccttc gctccatcag ccactgacct           gcccagcatg               901   cctgaacctg ccctgacctc ccgagcaaac atgacagagc acaagacgtc           ccccacccaa               961   tgcccggcag ctggagaggt ctccaacaag cttccaaaat ggcctgagcc           ggtggagcag               1021   ttctaccgct cactgcagga cacgtatggt gccgagcccg caggcccgga           tggcatccta               1081   gtggaggtgg atctggtgca ggccaggctg gagaggagca gcagcaagag           cctggagcgg               1141   gaactggcca ccccggactg ggcagaacgg cagctggccc aaggaggcct           ggctgaggtg               1201   ctgttggctg ccaaggagca ccggcggccg cgtgagacac gagtgattgc           tgtgctgggc               1261   aaagctggtc agggcaagag ctattgggct ggggcagtga gccgggcctg           ggcttgtggc               1321   cggcttcccc agtacgactt tgtcttctct gtcccctgcc attgcttgaa           ccgtccgggg               1381   gatgcctatg gcctgcagga tctgctcttc tccctgggcc cacagccact           cgtggcggcc               1441   gatgaggttt tcagccacat cttgaagaga cctgaccgcg ttctgctcat           cctagacggc               1501   ttcgaggagc tggaagcgca agatggcttc ctgcacagca cgtgcggacc           ggcaccggcg               1561   gagccctgct ccctccgggg gctgctggcc ggccttttcc agaagaagct           gctccgaggt               1621   tgcaccctcc tcctcacagc ccggccccgg ggccgcctgg tccagagcct           gagcaaggcc               1681   gacgccctat ttgagctgtc cggcttctcc atggagcagg cccaggcata           cgtgatgcgc               1741   tactttgaga gctcagggat gacagagcac caagacagag ccctgacgct           cctccgggac               1801   cggccacttc ttctcagtca cagccacagc cctactttgt gccgggcagt           gtgccagctc               1861   tcagaggccc tgctggagct tggggaggac gccaagctgc cctccacgct           cacgggactc               1921   tatgtcggcc tgctgggccg tgcagccctc gacagccccc ccggggccct           ggcagagctg               1981   gccaagctgg cctgggagct gggccgcaga catcaaagta ccctacagga           ggaccagttc               2041   ccatccgcag acgtgaggac ctgggcgatg gccaaaggct tagtccaaca           cccaccgcgg               2101   gccgcagagt ccgagctggc cttccccagc ttcctcctgc aatgcttcct           gggggccctg               2161   tggctggctc tgagtggcga aatcaaggac aaggagctcc cgcagtacct           agcattgacc               2221   ccaaggaaga agaggcccta tgacaactgg ctggagggcg tgccacgctt           tctggctggg               2281   ctgatcttcc agcctcccgc ccgctgcctg ggagccctac tcgggccatc           ggcggctgcc               2341   tcggtggaca ggaagcagaa ggtgcttgcg aggtacctga agcggctgca           gccggggaca               2401   ctgcgggcgc ggcagctgct ggagctgctg cactgcgccc acgaggccga           ggaggctgga               2461   atttggcagc acgtggtaca ggagctcccc ggccgcctct cttttctggg           cacccgcctc               2521   acgcctcctg atgcacatgt actgggcaag gccttggagg cggcgggcca           agacttctcc               2581   ctggacctcc gcagcactgg catttgcccc tctggattgg ggagcctcgt           gggactcagc               2641   tgtgtcaccc gtttcagggc tgccttgagc gacacggtgg cgctgtggga           gtccctgcag               2701   cagcatgggg agaccaagct acttcaggca gcagaggaga agttcaccat           cgagcctttc               2761   aaagccaagt ccctgaagga tgtggaagac ctgggaaagc ttgtgcagac           tcagaggacg               2821   agaagttcct cggaagacac agctggggag ctccctgctg ttcgggacct           aaagaaactg               2881   gagtttgcgc tgggccctgt ctcaggcccc caggctttcc ccaaactggt           gcggatcctc               2941   acggcctttt cctccctgca gcatctggac ctggatgcgc tgagtgagaa           caagatcggg               3001   gacgagggtg tctcgcagct ctcagccacc ttcccccagc tgaagtcctt           ggaaaccctc               3061   aatctgtccc agaacaacat cactgacctg ggtgcctaca aactcgccga           ggccctgcct               3121   tcgctcgctg catccctgct caggctaagc ttgtacaata actgcatctg           cgacgtggga               3181   gccgagagct tggctcgtgt gcttccggac atggtgtccc tccgggtgat           ggacgtccag               3241   tacaacaagt tcacggctgc cggggcccag cagctcgctg ccagccttcg           gaggtgtcct               3301   catgtggaga cgctggcgat gtggacgccc accatcccat tcagtgtcca           ggaacacctg               3361   caacaacagg attcacggat cagcctgaga t            
C2TA Protein ( Homo sapiens )
 
         [0000]                                      SEQ ID NO: 48                1   mrclaprpag sylsepqgss qcatmelgpl eggylellns dadplclyhf               ydqmdlagee               61   eielysepdt dtincdqfsr llcdmegdee treayaniae ldqyvfqdsq           leglskdifk               121   higpdevige smempaevgq ksqkrpfpee lpadlkhwkp aepptvvtgs           llvgpvsdcs               181   tlpclplpal fnqepasgqm rlektdqipm pfsssslscl nlpegpiqfv           ptistlphgl               241   wqiseagtgv ssifiyhgev pqasqvppps gftvhglpts pdrpgstspf           apsatdlpsm               301   pepaltsran mtehktsptq cpaagevsnk lpkwpepveq fyrslqdtyg           aepagpdgil               361   vevdlvqarl ersssksler elatpdwaer qlaqgglaev llaakehrrp           retrviavlg               421   kagqgksywa gavsrawacg rlpqydfvfs vpchclnrpg dayglqdllf           slgpqplvaa               481   devfshilkr pdrvllildg feeleaqdgf lhstcgpapa epcslrglla           glfqkkllrg               541   ctllltarpr grlvqslska dalfelsgfs meqaqayvmr yfessgmteh           qdraltllrd               601   rplllshshs ptlcravcql seallelged aklpstltgl yvgllgraal           dsppgalael               661   aklawelgrr hqstlqedqf psadvrtwam akglvqhppr aaeselafps           fllqcflgal               721   wlalsgeikd kelpqylalt prkkrpydnw legvprflag lifqpparcl           gallgpsaaa               781   svdrkqkvla rylkrlqpgt lrarqllell hcaheaeeag iwqhvvqelp           grlsflgtrl               841   tppdahvlgk aleaagqdfs ldlrstgicp sglgslvgls cvtrfraals           dtvalweslq               901   qhgetkllqa aeekftiepf kakslkdved lgklvqtqrt rsssedtage           lpavrdlkkl               961   efalgpvsgp qafpklvril tafsslqhld ldalsenkig degvsqlsat           fpqlksletl               1021   nlsqnnitdl gayklaealp slaasllrls lynncicdvg aeslarvlpd           mvslrvmdvq               1081   ynkftaagaq qlaaslrrcp hvetlamwtp tipfsvqehl qqqdsrislr            
Mxi1 cDNA ( Homo sapiens )
 
         [0000]                              SEQ ID NO: 49            1   atggagcggg tgaagatgat caacgtgcag cgtctgctgg           aggctgccga gtttttggag               61   cgccgggagc gagagtgtga acatggctac gcctcttcat           tcccgtccat gccgagcccc               121   cgactgcagc attcaaagcc cccacggagg ttgagccggg           cacagaaaca cagcagcggg               181   agcagcaaca ccagcactgc caacagatct acacacaatg           agctggaaaa gaatcgacga               241   gctcatctgc gcctttgttt agaacgctta aaagttctga           ttccactagg accagactgc               301   acccggcaca caacacttgg tttgctcaac aaagccaaag           cacacatcaa gaaacttgaa               361   gaagctgaaa gaaaaagcca gcaccagctc gagaatttgg           aacgagaaca gagattttta               421   aagtggcgac tggaacagct gcagggtcct caggagatgg           aacgaatacg aatggacagc               481   attggatcaa ctatttcttc agatcgttct gattcagagc           gagaggagat tgaagtggat               541   gttgaaagca cagagttctc ccatggagaa gtggacaata           taagtaccac cagcatcagt               601   gacattgatg accacagcag cctgccgagt attgggagtg           acgagggtta ctccagtgcc               661   agtgtcaaac tttcattcac ttcatag            
MXI1 Protein ( Homo sapiens )
 
         [0000]                              SEQ ID NO: 50            1   mervkminvq rlleaaefle rrerecehgy assfpsmpsp           rlqhskpprr lsraqkhssg               61   ssntstanrs thneleknrr ahlrlclerl kvliplgpdc           trhttlglln kakahikkle               121   eaerksqhql enlereqrfl kwrleqlqgp qemerirmds           igstissdrs dsereeievd               181   vestefshge vdnisttsis diddhsslps igsdegyssa           svklsfts            
Hes3 cDNA ( Homo sapiens )
 
         [0000]                              SEQ ID NO: 51            1   atggagaaaa agcgccgggc acgcatcaat gtgtcactgg           agcagctcaa gtcgctgctg               61   gagaaacact actcgcacca gatccggaag cgcaaattgg           agaaggccga catcctggag               121   ttgagcgtga agtacatgag aagccttcag aactccttgc           aagggctctg gcctgtgccc               181   aggggagccg agcaaccgtc gggcttccgc agctgcctgc           ccggcgtgag ccagctcctt               241   cggcgcggag atgaggtcgg cagcggcctg cgctgccccc           tggtgcccga gagcgccgcc               301   ggcagcacca tggacagcgc cgggttgggc caggaggcgc           ccgcgctgtt ccgcccttgc               361   acccctgccg tctgggctcc tgctccggcc gccggcggcc           cgcggtcccc accacccctg               421   ctcctcctcc ccgaaagtct ccctggctcg tccgccagcg           tccccccgcc gcagccagcg               481   tcgagtcgct gcgccgagag tcccgggctg ggcctgcgcg           tgtggcggcc ctggggaagc               541   cccggggatg acctgaactg a            
HES3 Protein ( Homo sapiens )
 
         [0000]                              SEQ ID NO: 52            1   mekkrrarin vsleqlksll ekhyshqirk rklekadile           lsvkymrslq nslqglwpvp               61   rgaeqpsgfr sclpgvsqll rrgdevgsgl rcplvpesaa           gstmdsaglg qeapalfrpc               121   tpavwapapa aggprspppl lllpeslpgs sasvpppqpa           ssrcaespgl glrvwrpwgs               181   pgddln            
Rpl22 cDNA ( Homo sapiens )
 
         [0000]                              SEQ ID NO: 53            1   atggctcctg tgaaaaagct tgtggtgaag gggggcaaaa           aaaagaagca agttctgaag               61   ttcactcttg attgcaccca ccctgtagaa gatggaatca           tggatgctgc caattttgag               121   cagtttttgc aagaaaggat caaagtgaac ggaaaagctg           ggaaccttgg tggaggggtg               181   gtgaccatcg aaaggagcaa gagcaagatc accgtgacat           ccgaggtgcc tttctccaaa               241   aggtatttga aatatctcac caaaaaatat ttgaagaaga           ataatctacg tgactggttg               301   cgcgtagttg ctaacagcaa agagagttac gaattacgtt           acttccagat taaccaggac               361   gaagaagagg aggaagacga ggattaa            
RPL22 Protein ( Homo sapiens )
 
         [0000]                              SEQ ID NO: 54            1   mapvkklvvk ggkkkkqvlk ftldcthpve dgimdaanfe           qflqerikvn gkagnlgggv               61   vtierskski tvtsevpfsk rylkyltkky lkknnlrdwl           rvvanskesy elryfqinqd               121   eeeeeded            
Chd5 cDNA ( Homo sapiens )
 
         [0000]                                      SEQ ID NO: 55                1   atgcggggcc cagtgggcac cgaggaggag ctgccgcggc tgttcgccga               ggagatggag               61   aatgaggacg agatgtcaga agaagaagat ggtggtcttg aagccttcga           tgactttttc               121   cctgtggagc ccgtgagcct tcctaagaag aagaaaccca agaagctcaa           ggaaaacaag               181   tgtaaaggga agcggaagaa gaaagagggg agcaatgatg agctatcaga           gaatgaagag               241   gatctggaag agaagtcgga gagtgaaggc agtgactact ccccgaataa           aaagaagaag               301   aagaaactca aggacaagaa ggagaaaaaa gccaagcgaa aaaagaagga           tgaggatgag               361   gatgataatg atgatggatg cttaaaggag cccaagtcct cggggcagct           catggccgag               421   tggggcctgg acgacgtgga ctacctgttc tcggaggagg attaccacac           gctgaccaac               481   tacaaggcct tcagccagtt cctcaggcca ctcattgcca agaagaaccc           gaagatcccc               541   atgtccaaaa tgatgaccgt cctgggtgcc aagtggcggg agttcagcgc           caacaacccc               601   ttcaagggca gctccgcggc agcagcggcg gcggcggtgg ctgcggctgt           agagacggtc               661   accatctccc ctccgctagc cgtcagcccc ccgcaggtgc cccagcctgt           gcctatccgc               721   aaggccaaga ccaaggaggg caaagggcct ggagtgagga agaagatcaa           aggctccaaa               781   gatgggaaga aaaagggcaa agggaaaaag acggccgggc tcaagttccg           cttcgggggg               841   atcagcaaca agaggaagaa aggctcctcg agtgaagaag atgagaggga           ggagtcggac               901   ttcgacagcg ccagcatcca cagtgcctcc gtgcgctccg aatgctctgc           agccctgggc               961   aagaagagca agaggaggcg caagaagaag aggattgatg atggtgacgg           ctatgagaca               1021   gaccaccagg attactgtga ggtgtgccag cagggtgggg agatcatcct           gtgcgacacc               1081   tgcccgaggg cctaccatct cgtatgcctg gacccagagc tggagaaggc           tcccgagggc               1141   aagtggagct gcccccactg tgagaaggag gggatccagt gggagccgaa           ggacgacgac               1201   gatgaagagg aggagggcgg ctgcgaggag gaggaggacg accacatgga           gttctgccgc               1261   gtgtgcaagg acgggggcga gctgctctgc tgcgacgcct gcccctcctc           ctaccacctg               1321   cattgcctca acccgccgct gcccgagatc ccaaacggtg aatggctctg           cccgcgctgt               1381   acttgccccc cactgaaggg caaagtccag cggattctac actggaggtg           gacggagccc               1441   cctgccccct tcatggtggg gctgccgggg cctgacgtgg agcccagcct           ccctccacct               1501   aagcccctgg agggcatccc tgagagagag ttctttgtca agtgggcagg           gctgtcctac               1561   tggcattgct cctgggtgaa ggagctacag ctggagctgt accacacggt           gatgtatcgc               1621   aactaccaaa gaaagaacga catggatgag ccgcccccct ttgactacgg           ctctggggat               1681   gaagacggca agagcgagaa gaggaagaac aaggaccccc tctatgccaa           gatggaggag               1741   cgcttctacc gctatggcat caagccagag tggatgatga ttcaccgaat           cctgaaccat               1801   agctttgaca agaaggggga tgtgcactac ctgatcaagt ggaaagacct           gccctacgac               1861   cagtgcacct gggagatcga tgacatcgac atcccctact acgacaacct           caagcaggcc               1921   tactggggcc acagggagct gatgctggga gaagacacca ggctgcccaa           gaggctgctc               1981   aagaagggca agaagctgag ggacgacaag caggagaagc cgccggacac           gcccattgtg               2041   gaccccacgg tcaagttcga caagcagcca tggtacatcg actccacagg           cggcacactg               2101   cacccgtacc agctggaggg cctcaactgg ctgcgcttct cttgggccca           gggcactgac               2161   accatcctgg ccgatgagat gggtctgggc aagacggtgc agaccatcgt           gttcctttac               2221   tccctctaca aggagggcca ctccaaaggg ccctacctgg ttagcgcgcc           cctctccacc               2281   atcatcaact gggaacgcga gtttgagatg tgggcgcccg acttctacgt           ggtcacctac               2341   acgggggaca aggagagccg ctcggtgatt cgggagaacg agttttcctt           tgaggacaac               2401   gccattcgga gtgggaagaa ggtattccgt atgaagaaag aagtgcagat           caaattccac               2461   gtgctgctca cctcctatga gctcatcacc attgaccagg ccatcctggg           ctccatcgag               2521   tgggcctgcc tggtggtaga tgaggcccac cgcctcaaga acaaccagtc           caagtttttt               2581   agggtcttaa acagctacaa gattgattac aagctgctgc tgacagggac           cccccttcag               2641   aacaacctgg aggagctgtt ccatctcctc aacttcctga ctccagagag           gttcaacaac               2701   ctggagggct tcctggagga gtttgctgac atctccaagg aagaccagat           caagaagctg               2761   catgacctgc tggggccgca catgctcagg cggctcaagg ctgacgtgtt           caagaacatg               2821   ccggccaaga ccgagctcat tgtccgggtg gagctgagcc agatgcagaa           gaagtactac               2881   aagttcatcc tcacacggaa ctttgaggca ctgaactcca aggggggcgg           gaaccaagta               2941   tcgctgctca acatcatgat ggacctgaaa aagtgctgca accaccccta           cctcttccct               3001   gtggctgccg tggaggcccc tgtcttgccc aatggctcct acgatggaag           ctccctggtc               3061   aagtcttcag ggaagctcat gctgctacag aagatgctga agaaactgcg           ggatgagggg               3121   caccgtgtgc tcatcttctc ccagatgacc aagatgctgg acctcctgga           ggacttcctg               3181   gagtacgaag gctacaagta tgagcggatt gatggtggca tcaccggggg           cctccggcag               3241   gaggcaatcg acagattcaa tgcccccggg gcccagcagt tctgcttcct           cctctcaacc               3301   cgggcaggtg gtctgggcat caacctggcc acggcggaca ctgtcatcat           ctacgactcg               3361   gactggaacc cgcacaatga catccaggcc ttcagccgcg cccaccgcat           cggccagaac               3421   aagaaggtga tgatctaccg cttcgtgact cgggcctcgg tggaggagcg           catcacgcag               3481   gtggccaagc gcaagatgat gctcacccac ctggtggtgc ggcccggcct           cggctccaag               3541   tcggggtcca tgaccaagca ggagctggac gacatcctca agttcggcac           ggaggaactc               3601   ttcaaggacg acgtggaggg catgatgtct cagggccaga ggccggtcac           acccatccct               3661   gatgtccagt cctccaaagg ggggaacttg gccgccagtg caaagaagaa           gcacggtagc               3721   accccgccag gtgacaacaa ggacgtggag gacagcagtg tgatccacta           tgacgatgcg               3781   gccatctcca agctgctgga ccggaaccag gacgctacag atgacacgga           gctacagaac               3841   atgaacgagt acctgagctc cttcaaggtg gcgcagtacg tggtgcgcga           ggaggacggc               3901   gtggaggagg tggagcggga aatcatcaag caggaggaga acgtggaccc           cgactactgg               3961   gagaagctgc tgcggcacca ctatgagcag cagcaggagg acctggcccg           caacctgggc               4021   aagggcaagc gcatccgcaa gcaggtcaac tacaacgatg cctcccagga           ggaccaggag               4081   tggcaggatg agctctctga taaccagtca gaatattcca ttggctctga           ggatgaggat               4141   gaggactttg aagagaggcc ggaagggcag agtggacgac gacaatcccg           gaggcagctg               4201   aagagtgaca gggacaagcc cctgcccccg cttctcgccc gagttggtgg           caacatcgag               4261   gtgctgggct tcaatgcccg acagcggaag gcctttctga acgccatcat           gcgctggggc               4321   atgcccccgc aggacgcctt caactcccac tggctggtgc gggaccttcg           agggaagagc               4381   gagaaggagt ttagagccta tgtgtccctc ttcatgcggc acctgtgtga           gccgggggcg               4441   gatggtgcag agaccttcgc agacggcgtg ccccgggagg gcctctccag           gcagcacgtg               4501   ctgacccgca tcggggtcat gtcactagtt aggaagaagg ttcaggagtt           tgagcatgtc               4561   aacgggaagt acagcacccc agacttgatc cctgaggggc ccgaggggaa           gaagtcgggc               4621   gaggtgatct cctcggaccc caacacacca gtgcccgcca gccctgccca           cctcctgcca               4681   gccccgctgg gcctgccaga caaaatggaa gcccagctgg gctacatgga           tgagaaagac               4741   cccggggcac agaagccaag gcagcccctg gaagtccagg cccttccagc           cgccttggat               4801   agagtggaga gtgaggacaa gcacgagagc ccagccagca aggagagagc           ccgagaggag               4861   cggccagagg agacggagaa ggccccgccc tccccggagc agctgccgag           agaggaggtg               4921   cttcctgaga aggagaagat cctggacaag ctggagctga gcttgatcca           cagcagaggg               4981   gacagttccg aactcaggcc agatgacacc aaggctgagg agaaggagcc           cattgaaaca               5041   cagcaaaatg gtgacaaaga ggaagatgac gaggggaaga aggaggacaa           gaaggggaaa               5101   ttcaagttca tgttcaacat cgcggacggg ggcttcacgg agttgcacac           gctgtggcag               5161   aacgaggagc gggctgctgt atcctctggg aaaatctacg acatctggca           ccggcgccat               5221   gactactggc tgctggcggg catcgtgacg cacggctacg cccgctggca           ggacatccag               5281   aatgacccac ggtacatgat cctcaacgag cccttcaagt ctgaggtcca           caagggcaac               5341   tacctggaga tgaagaacaa gttcctggcc cgcaggttta agctgctgga           gcaggcgttg               5401   gtcattgagg agcagctccg gagggccgcg tacctgaaca tgacgcagga           ccccaaccac               5461   cccgccatgg ccctcaacgc ccgcctggct gaagtggagt gcctcgccga           gagccaccag               5521   cacctgtcca aggagtccct tgctgggaac aagcctgcca atgccgtcct           gcacaaggtc               5581   ctgaaccagc tggaggagct gctgagcgac atgaaggccg acgtgacccg           gctgccatcc               5641   atgctgtccc gcatcccccc ggtggccgcc cggctgcaga tgtcggagcg           cagcatcctg               5701   agccgcctga ccaaccgcgc cggggacccc accatccagc agggcgcttt           cggctcctcc               5761   cagatgtaca gcaacaactt tgggcccaac ttccggggcc ctggaccggg           agggattgtc               5821   aactacaacc agatgcccct ggggccctat gtgaccgata tctag            
CHD5 Protein ( Homo sapiens )
 
         [0000]                                      SEQ ID NO: 56                1   mrgpvgteee lprlfaeeme nedemseeed ggleafddff pvepvslpkk               kkpkklkenk               61   ckgkrkkkeg sndelsenee dleekseseg sdyspnkkkk kklkdkkekk           akrkkkdede               121   ddnddgclke pkssgqlmae wglddvdylf seedyhtltn ykafsqflrp           liakknpkip               181   mskmmtvlga kwrefsannp fkgssaaaaa aavaaavetv tispplavsp           pqvpqpvpir               241   kaktkegkgp gvrkkikgsk dgkkkgkgkk taglkfrfgg isnkrkkgss           seedereesd               301   fdsasihsas vrsecsaalg kkskrrrkkk riddgdgyet dhqdycevcq           qggeiilcdt               361   cprayhlvcl dpelekapeg kwscphceke giqwepkddd deeeeggcee           eeddhmefcr               421   vckdggellc cdacpssyhl hclnpplpei pngewlcprc tcpplkgkvq           rilhwrwtep               481   papfmvglpg pdvepslppp kplegipere ffvkwaglsy whcswvkelq           lelyhtvmyr               541   nyqrkndmde pppfdygsgd edgksekrkn kdplyakmee rfyrygikpe           wmmihrilnh               601   sfdkkgdvhy likwkdlpyd qctweiddid ipyydnlkqa ywghrelmlg           edtrlpkrll               661   kkgkklrddk qekppdtpiv dptvkfdkqp wyidstggtl hpyqleglnw           lrfswaqgtd               721   tilademglg ktvqtivfly slykeghskg pylvsaplst iinwerefem           wapdfyvvty               781   tgdkesrsvi renefsfedn airsgkkvfr mkkevqikfh vlltsyelit           idqailgsie               841   waclvvdeah rlknnqskff rvlnsykidy kllltgtplq nnleelfhll           nfltperfnn               901   legfleefad iskedqikkl hdllgphmlr rlkadvfknm paktelivrv           elsqmqkkyy               961   kfiltrnfea lnskgggnqv sllnimmdlk kccnhpylfp vaaveapvlp           ngsydgsslv               1021   kssgklmllq kmlkklrdeg hrvlifsqmt kmldlledfl eyegykyeri           dggitgglrq               1081   eaidrfnapg aqqfcfllst ragglginla tadtviiyds dwnphndiqa           fsrahrigqn               1141   kkvmiyrfvt rasveeritq vakrkmmlth lvvrpglgsk sgsmtkqeld           dilkfgteel               1201   fkddvegmms qgqrpvtpip dvqsskggnl aasakkkhgs tppgdnkdve           dssvihydda               1261   aisklldrnq datddtelqn mneylssfkv aqyvvreedg veevereiik           qeenvdpdyw               1321   ekllrhhyeq qqedlarnlg kgkrirkqvn yndasqedqe wqdelsdnqs           eysigseded               1381   edfeerpegq sgrrqsrrql ksdrdkplpp llarvggnie vlgfnarqrk           aflnaimrwg               1441   mppqdafnsh wlvrdlrgks ekefrayvsl fmrhlcepga dgaetfadgv           preglsrqhv               1501   ltrigvmslv rkkvqefehv ngkystpdli pegpegkksg evissdpntp           vpaspahllp               1561   aplglpdkme aqlgymdekd pgaqkprqpl evqalpaald rvesedkhes           paskeraree               1621   rpeetekapp speqlpreev lpekekildk lelslihsrg dsselrpddt           kaeekepiet               1681   qqngdkeedd egkkedkkgk fkfmfniadg gftelhtlwq neeraavssg           kiydiwhrrh               1741   dywllagivt hgyarwqdiq ndprymilne pfksevhkgn ylemknkfla           rrfklleqal               1801   vieeqlrraa ylnmtqdpnh pamalnarla eveclaeshq hlskeslagn           kpanavlhkv               1861   lnqleellsd mkadvtrlps mlsrippvaa rlqmsersil srltnragdp           tiqqgafgss               1921   qmysnnfgpn frgpgpggiv nynqmplgpy vtdi            
Ikaros cDNA ( Homo sapiens )
 
         [0000]                                      SEQ ID NO: 57                1   atggatgctg atgagggtca agacatgtcc caagtttcag ggaaggaaag               cccccctgta               61   agcgatactc cagatgaggg cgatgagccc atgccgatcc ccgaggacct           ctccaccacc               121   tcgggaggac agcaaagctc caagagtgac agagtcgtgg ccagtaatgt           taaagtagag               181   actcagagtg atgaagagaa tgggcgtgcc tgtgaaatga atggggaaga           atgtgcggag               241   gatttacgaa tgcttgatgc ctcgggagag aaaatgaatg gctcccacag           ggaccaaggc               301   agctcggctt tgtcgggagt tggaggcatt cgacttccta acggaaaact           aaagtgtgat               361   atctgtggga tcatttgcat cgggcccaat gtgctcatgg ttcacaaaag           aagccacact               421   ggagaacggc ccttccagtg caatcagtgc ggggcctcat tcacccagaa           gggcaacctg               481   ctccggcaca tcaagctgca ttccggggag aagcccttca aatgccacct           ctgcaactac               541   gcctgccgcc ggagggacgc cctcactggc cacctgagga cgcactccgt           tggtaaacct               601   cacaaatgtg gatattgtgg ccgaagctat aaacagcgaa gctctttaga           ggaacataaa               661   gagcgctgcc acaactactt ggaaagcatg ggccttccgg gcacactgta           cccagtcatt               721   aaagaagaaa ctaatcacag tgaaatggca gaagacctgt gcaagatagg           atcagagaga               781   tctctcgtgc tggacagact agcaagtaac gtcgccaaac gtaagagctc           tatgcctcag               841   aaatttcttg gggacaaggg cctgtccgac acgccctacg acagcagcgc           cagctacgag               901   aaggagaacg aaatgatgaa gtcccacgtg atggaccaag ccatcaacaa           cgccatcaac               961   tacctggggg ccgagtccct gcgcccgctg gtgcagacgc ccccgggcgg           ttccgaggtg               1021   gtcccggtca tcagcccgat gtaccagctg cacaagccgc tcgcggaggg           caccccgcgc               1081   tccaaccact cggcccagga cagcgccgtg gagaacctgc tgctgctctc           caaggccaag               1141   ttggtgccct cggagcgcga ggcgtccccg agcaacagct gccaagactc           cacggacacc               1201   gagagcaaca acgaggagca gcgcagcggt ctcatctacc tgaccaacca           catcgccccg               1261   cacgcgcgca acgggctgtc gctcaaggag gagcaccgcg cctacgacct           gctgcgcgcc               1321   gcctccgaga actcgcagga cgcgctccgc gtggtcagca ccagcgggga           gcagatgaag               1381   gtgtacaagt gcgaacactg ccgggtgctc ttcctggatc acgtcatgta           caccatccac               1441   atgggctgcc acggcttccg tgatcctttt gagtgcaaca tgtgcggcta           ccacagccag               1501   gaccggtacg agttctcgtc gcacataacg cgaggggagc accgcttcca           catgagctaa            
IKAROS Protein ( Homo sapiens )
 
         [0000]                                      SEQ ID NO: 58                1   mdadegqdms qvsgkesppv sdtpdegdep mpipedlstt sggqqssksd               rvvasnvkve               61   tqsdeengra cemngeecae dlrmldasge kmngshrdqg ssalsgvggi           rlpngklkcd               121   icgiicigpn vlmvhkrsht gerpfqcnqc gasftqkgnl lrhiklhsge           kpfkchlcny               181   acrrrdaltg hlrthsvgkp hkcgycgrsy kqrssleehk erchnylesm           glpgtlypvi               241   keetnhsema edlckigser slvldrlasn vakrkssmpq kflgdkglsd           tpydssasye               301   kenemmkshv mdqainnain ylgaeslrpl vqtppggsev vpvispmyql           hkplaegtpr               361   snhsaqdsav enllllskak lvpsereasp snscqdstdt esnneeqrsg           liyltnhiap               421   harnglslke ehraydllra asensqdalr vvstsgeqmk vykcehcrvl           fldhvmytih               481   mgchgfrdpf ecnmcgyhsq dryefsshit rgehrfhms            
Ptprn2 cDNA ( Homo sapiens )
 
         [0000]                                      SEQ ID NO: 59                1   atggggccgc cgctcccgct gctgctgctg ctactgctgc tgctgccgcc               acgcgtcctg               61   cctgccgccc cttcgtccgt cccccgcggc cggcagctcc cggggcgtct           gggctgcctg               121   ctcgaggagg gcctctgcgg agcgtccgag gcctgtgtga acgatggagt           gtttggaagg               181   tgccagaagg ttccggcaat ggacttttac cgctacgagg tgtcgcccgt           ggccctgcag               241   cgcctgcgcg tggcgttgca gaagctttcc ggcacaggtt tcacgtggca           ggatgactat               301   actcagtatg tgatggacca ggaacttgca gacctcccga aaacctacct           gaggcgtcct               361   gaagcatcca gcccagccag gccctcaaaa cacagcgttg gcagcgagag           gaggtacagt               421   cgggagggcg gtgctgccct ggccaacgcc ctccgacgcc acctgccctt           cctggaggcc               481   ctgtcccagg ccccagcctc agacgtgctc gccaggaccc atacggcgca           ggacagaccc               541   cccgctgagg gtgatgaccg cttctccgag agcatcctga cctatgtggc           ccacacgtct               601   gcgctgacct accctcccgg gccccggacc cagctccgcg aggacctcct           gccgcggacc               661   ctcggccagc tccagccaga tgagctcagc cctaaggtgg acagtggtgt           ggacagacac               721   catctgatgg cggccctcag tgcctatgct gcccagaggc ccccagctcc           ccccggggag               781   ggcagcctgg agccacagta ccttctgcgt gcaccctcaa gaatgcccag           gcctttgctg               841   gcaccagccg ccccccagaa gtggccttca cctctgggag attccgaaga           cccctccagc               901   acaggcgatg gagcacggat tcataccctc ctgaaggacc tgcagaggca           gccggctgag               961   gtgaggggcc tgagtggcct ggagctggac ggcatggctg agctgatggc           tggcctgatg               1021   caaggcgtgg accatggagt agctcgaggc agccctggga gagcggccct           gggagagtct               1081   ggagaacagg cggatggccc caaggccacc ctccgtggag acagctttcc           agatgacgga               1141   gtgcaggacg acgatgatag actttaccaa gaggtccatc gtctgagtgc           cacactcggg               1201   ggcctcctgc aggaccacgg gtctcgactc ttacctggag ccctcccctt           tgcaaggccc               1261   ctcgacatgg agaggaagaa gtccgagcac cctgagtctt ccctgtcttc           agaagaggag               1321   actgccggag tggagaacgt caagagccag acgtattcca aagatctgct           ggggcagcag               1381   ccgcattcgg agcccggggc cgctgcgttt ggggagctcc aaaaccagat           gcctgggccc               1441   tcgaaggagg agcagagcct tccagcgggt gctcaggagg ccctcagcga           cggcctgcaa               1501   ttggaggtcc agccttccga ggaagaggcg cggggctaca tcgtgacaga           cagagacccc               1561   ctgcgccccg aggaaggaag gcggctggtg gaggacgtcg cccgcctcct           gcaggtgccc               1621   agcagtgcgt tcgctgacgt ggaggttctc ggaccagcag tgaccttcaa           agtgagcgcc               1681   aatgtccaaa acgtgaccac tgaggatgtg gagaaggcca cagttgacaa           caaagacaaa               1741   ctggaggaaa cctctggact gaaaattctt caaaccggag tcgggtcgaa           aagcaaactc               1801   aagttcctgc ctcctcaggc ggagcaagaa gactccacca agttcatcgc           gctcaccctg               1861   gtctccctcg cctgcatcct gggcgtcctc ctggcctctg gcctcatcta           ctgcctccgc               1921   catagctctc agcacaggct gaaggagaag ctctcgggac tagggggcga           cccaggtgca               1981   gatgccactg ccgcctacca ggagctgtgc cgccagcgta tggccacgcg           gccaccagac               2041   cgacctgagg gcccgcacac gtcacgcatc agcagcgtct catcccagtt           cagcgacggg               2101   ccgatcccca gcccctccgc acgcagcagc gcctcatcct ggtccgagga           gcctgtgcag               2161   tccaacatgg acatctccac cggccacatg atcctgtcct acatggagga           ccacctgaag               2221   aacaagaacc ggctggagaa ggagtgggaa gcgctgtgcg cctaccaggc           ggagcccaac               2281   agctcgttcg tggcccagag ggaggagaac gtgcccaaga accgctccct           ggctgtgctg               2341   acctatgacc actcccgggt cctgctgaag gcggagaaca gccacagcca           ctcagactac               2401   atcaacgcta gccccatcat ggatcacgac ccgaggaacc ccgcgtacat           cgccacccag               2461   ggaccgctgc ccgccaccgt ggctgacttt tggcagatgg tgtgggagag           cggctgcgtg               2521   gtgatcgtca tgctgacacc cctcgcggag aacggcgtcc ggcagtgcta           ccactactgg               2581   ccggatgaag gctccaatct ctaccacatc tatgaggtga acctggtctc           cgagcacatc               2641   tggtgtgagg acttcctggt gaggagcttc tatctgaaga acctgcagac           caacgagacg               2701   cgcaccgtga cgcagttcca cttcctgagt tggtatgacc gaggagtccc           ttcctcctca               2761   aggtccctcc tggacttccg cagaaaagta aacaagtgct acaggggccg           ttcttgtcca               2821   ataattgttc attgcagtga cggtgcaggc cggagcggca cctacgtcct           gatcgacatg               2881   gttctcaaca agatggccaa aggtgctaaa gagattgata tcgcagcgac           cctggagcac               2941   ttgagggacc agagacccgg catggtccag acgaaggagc agtttgagtt           cgcgctgaca               3001   gccgtggctg aggaggtgaa cgccatcctc aaggcccttc cccagtga            
PTPRN2 Protein ( Homo sapiens )
 
         [0000]                                      SEQ ID NO: 60                1   mgpplpllll lllllpprvl paapssvprg rqlpgrlgcl leeglcgase               acvndgvfgr               61   cqkvpamdfy ryevspvalq rlrvalqkls gtgftwqddy tqyvmdqela           dlpktylrrp               121   eassparpsk hsvgserrys reggaalana lrrhlpflea lsqapasdvl           arthtaqdrp               181   paegddrfse siltyvahts altyppgprt qlredllprt lgqlqpdels           pkvdsgvdrh               241   hlmaalsaya aqrppappge gslepqyllr apsrmprpll apaapqkwps           plgdsedpss               301   tgdgarihtl lkdlqrqpae vrglsgleld gmaelmaglm qgvdhgvarg           spgraalges               361   geqadgpkat lrgdsfpddg vqddddrlyq evhrlsatlg gllqdhgsrl           lpgalpfarp               421   ldmerkkseh pesslsseee tagvenvksq tyskdllgqq phsepgaaaf           gelqnqmpgp               481   skeeqslpag aqealsdglq levqpseeea rgyivtdrdp lrpeegrrlv           edvarllqvp               541   ssafadvevl gpavtfkvsa nvqnvttedv ekatvdnkdk leetsglkil           qtgvgskskl               601   kflppqaeqe dstkfialtl vslacilgvl lasgliyclr hssqhrlkek           lsglggdpga               661   dataayqelc rqrmatrppd rpegphtsri ssvssqfsdg pipspsarss           asswseepvq               721   snmdistghm ilsymedhlk nknrlekewe alcayqaepn ssfvaqreen           vpknrslavl               781   tydhsrvllk aenshshsdy inaspimdhd prnpayiatq gplpatvadf           wqmvwesgcv               841   vivmltplae ngvrqcyhyw pdegsnlyhi yevnlvsehi wcedflvrsf           ylknlqtnet               901   rtvtqfhfls wydrgvpsss rslldfrrkv nkcyrgrscp iivhcsdgag           rsgtyvlidm               961   vlnkmakgak eidiaatleh lrdqrpgmvq tkeqfefalt avaeevnail           kalpq            
Tcrb cDNA (Partial Sequence) ( Homo sapiens )
 
         [0000]                                      SEQ ID NO: 61                1   atgggctgaa gtctccactg tggtgtggtc cattgtctca ggctccatgg               atactggaat               61   tacccagaca ccaaaatacc tggtcacagc aatggggagt aaaaggacaa           tgaaacgtga               121   gcatctggga catgattcta tgtattggta cagacagaaa gctaagaaat           ccctggagtt               181   catgttttac tacaactgta aggaattcat tgaaaacaag actgtgccaa           atcacttcac               241   acctgaatgc cctgacagct ctcgcttata ccttcatgtg gtcgcactgc           agcaagaaga               301   ctcagctgcg tatctctgca ccagcagcca aga            
TCRB Protein ( Homo sapiens )
 
         [0000]                                      SEQ ID NO: 62                1   mgtsllcwma lcllgadhad tgvsqnprhn itkrgqnvtf rcdpisehnr               lywyrqtlgq               61   gpefltyfqn eaqleksrll sdrfsaerpk gsfstleiqr teqgdsamyl           casslaglnq               121   pqhfgdgtrl sil            
Gnaq cDNA ( Homo sapiens )
 
         [0000]                                      SEQ ID NO: 63                1   atgactctgg agtccatcat ggcgtgctgc ctgagcgagg aggccaagga               agcccggcgg               61   atcaacgacg agatcgagcg gcagctccgc agggacaagc gggacgcccg           ccgggagctc               121   aagctgctgc tgctcgggac aggagagagt ggcaagagta cgtttatcaa           gcagatgaga               181   atcatccatg ggtcaggata ctctgatgaa gataaaaggg gcttcaccaa           gctggtgtat               241   cagaacatct tcacggccat gcaggccatg atcagagcca tggacacact           caagatccca               301   tacaagtatg agcacaataa ggctcatgca caattagttc gagaagttga           tgtggagaag               361   gtgtctgctt ttgagaatcc atatgtagat gcaataaaga gtttatggaa           tgatcctgga               421   atccaggaat gctatgatag acgacgagaa tatcaattat ctgactctac           caaatactat               481   cttaatgact tggaccgcgt agctgaccct gcctacctgc ctacgcaaca           agatgtgctt               541   agagttcgag tccccaccac agggatcatc gaatacccct ttgacttaca           aagtgtcatt               601   ttcagaatgg tcgatgtagg gggccaaagg tcagagagaa gaaaatggat           acactgcttt               661   gaaaatgtca cctctatcat gtttctagta gcgcttagtg aatatgatca           agttctcgtg               721   gagtcagaca atgagaaccg aatggaggaa agcaaggctc tctttagaac           aattatcaca               781   tacccctggt tccagaactc ctcggttatt ctgttcttaa acaagaaaga           tcttctagag               841   gagaaaatca tgtattccca tctagtcgac tacttcccag aatatgatgg           accccagaga               901   gatgcccagg cagcccgaga attcattctg aagatgttcg tggacctgaa           cccagacagt               961   gacaaaatta tctactccca cttcacgtgc gccacagaca ccgagaatat           ccgctttgtc               1021   tttgctgccg tcaaggacac catcctccag ttgaacctga aggagtacaa           tctggtctaa            
GNAQ Protein ( Homo sapiens )
 
         [0000]                                      SEQ ID NO: 64                1   mtlesimacc lseeakearr indeierqlr rdkrdarrel kllllgtges               gkstfikqmr               61   iihgsgysde dkrgftklvy gniftamqam iramdtlkip ykyehnkaha           qlvrevdvek               121   vsafenpyvd aikslwndpg iqecydrrre yqlsdstkyy lndldrvadp           aylptqqdvl               181   rvrvpttgii eypfdlqsvi frmvdvggqr serrkwihcf envtsimflv           alseydqvlv               241   esdnenrmee skalfrtiit ypwfqnssvi lflnkkdlle ekimyshlvd           yfpeydgpqr               301   daqaarefil kmfvdlnpds dkiiyshftc atdtenirfv faavkdtilq           lnlkeynlv            
Pten cDNA ( Homo sapiens )
 
         [0000]                                      SEQ ID NO: 65                1   atgacagcca tcatcaaaga gatcgttagc agaaacaaaa ggagatatca               agaggatgga               61   ttcgacttag acttgaccta tatttatcca aacattattg ctatgggatt           tcctgcagaa               121   agacttgaag gcgtatacag gaacaatatt gatgatgtag taaggttttt           ggattcaaag               181   cataaaaacc attacaagat atacaatctt tgtgctgaaa gacattatga           caccgccaaa               241   tttaattgca gagttgcaca atatcctttt gaagaccata acccaccaca           gctagaactt               301   atcaaaccct tttgtgaaga tcttgaccaa tggctaagtg aagatgacaa           tcatgttgca               361   gcaattcact gtaaagctgg aaagggacga actggtgtaa tgatatgtgc           atatttatta               421   catcggggca aatttttaaa ggcacaagag gccctagatt tctatgggga           agtaaggacc               481   agagacaaaa agggagtaac tattcccagt cagaggcgct atgtgtatta           ttatagctac               541   ctgttaaaga atcatctgga ttatagacca gtggcactgt tgtttcacaa           gatgatgttt               601   gaaactattc caatgttcag tggcggaact tgcaatcctc agtttgtggt           ctgccagcta               661   aaggtgaaga tatattcctc caattcagga cccacacgac gggaagacaa           gttcatgtac               721   tttgagttcc ctcagccgtt acctgtgtgt ggtgatatca aagtagagtt           cttccacaaa               781   cagaacaaga tgctaaaaaa ggacaaaatg tttcactttt gggtaaatac           attcttcata               841   ccaggaccag aggaaacctc agaaaaagta gaaaatggaa gtctatgtga           tcaagaaatc               901   gatagcattt gcagtataga gcgtgcagat aatgacaagg aatatctagt           acttacttta               961   acaaaaaatg atcttgacaa agcaaataaa gacaaagcca accgatactt           ttctccaaat               1021   tttaaggtga agctgtactt cacaaaaaca gtagaggagc cgtcaaatcc           agaggctagc               1081   agttcaactt ctgtaacacc agatgttagt gacaatgaac ctgatcatta           tagatattct               1141   gacaccactg actctgatcc agagaatgaa ccttttgatg aagatcagca           tacacaaatt               1201   acaaaagtct ga            
PTEN Protein ( Homo sapiens )
 
         [0000]                                      SEQ ID NO: 66                1   mtaiikeivs rnkrryqedg fdldltyiyp niiamgfpae rlegvyrnni               ddvvrfldsk               61   hknhykiynl caerhydtak fncrvaqypf edhnppqlel ikpfcedldq           wlseddnhva               121   aihckagkgr tgvmicayll hrgkflkaqe aldfygevrt rdkkgvtips           qrryvyyysy               181   llknhldyrp vallfhkmmf etipmfsggt cnpqfvvcql kvkiyssnsg           ptrredkfmy               241   fefpqplpvc gdikveffhk qnkmlkkdkm fhfwvntffi pgpeetsekv           engslcdqei               301   dsicsierad ndkeylvltl tkndldkank dkanryfspn fkvklyftkt           veepsnpeas               361   sstsvtpdvs dnepdhyrys dttdsdpene pfdedqhtqi tkv            
Fbxw7 cDNA ( Homo sapiens )
 
         [0000]                                      SEQ ID NO: 67                1   atgaatcagg aactgctctc tgtgggcagc aaaagacgac gaactggagg               ctctctgaga               61   ggtaaccctt cctcaagcca ggtagatgaa gaacagatga atcgtgtggt           agaggaggaa               121   cagcaacagc aactcagaca acaagaggag gagcacactg caaggaatgg           tgaagttgtt               181   ggagtagaac ctagacctgg aggccaaaat gattcccagc aaggacagtt           ggaagaaaac               241   aataatagat ttatttcggt agatgaggac tcctcaggaa accaagaaga           acaagaggaa               301   gatgaagaac atgctggtga acaagatgag gaggatgagg aggaggagga           gatggaccag               361   gagagtgacg attttgatca gtctgatgat agtagcagag aagatgaaca           tacacatact               421   aacagtgtca cgaactccag tagtattgtg gacctgcccg ttcaccaact           ctcctcccca               481   ttctatacaa aaacaacaaa aatgaaaaga aagttggacc atggttctga           ggtccgctct               541   ttttctttgg gaaagaaacc atgcaaagtc tcagaatata caagtaccac           tgggcttgta               601   ccatgttcag caacaccaac aacttttggg gacctcagag cagccaatgg           ccaagggcaa               661   caacgacgcc gaattacatc tgtccagcca cctacaggcc tccaggaatg           gctaaaaatg               721   tttcagagct ggagtggacc agagaaattg cttgctttag atgaactcat           tgatagttgt               781   gaaccaacac aagtaaaaca tatgatgcaa gtgatagaac cccagtttca           acgagacttc               841   atttcattgc tccctaaaga gttggcactc tatgtgcttt cattcctgga           acccaaagac               901   ctgctacaag cagctcagac atgtcgctac tggagaattt tggctgaaga           caaccttctc               961   tggagagaga aatgcaaaga agaggggatt gatgaaccat tgcacatcaa           gagaagaaaa               1021   gtaataaaac caggtttcat acacagtcca tggaaaagtg catacatcag           acagcacaga               1081   attgatacta actggaggcg aggagaactc aaatctccta aggtgctgaa           aggacatgat               1141   gatcatgtga tcacatgctt acagttttgt ggtaaccgaa tagttagtgg           ttctgatgac               1201   aacactttaa aagtttggtc agcagtcaca ggcaaatgtc tgagaacatt           agtgggacat               1261   acaggtggag tatggtcatc acaaatgaga gacaacatca tcattagtgg           atctacagat               1321   cggacactca aagtgtggaa tgcagagact ggagaatgta tacacacctt           atatgggcat               1381   acttccactg tgcgttgtat gcatcttcat gaaaaaagag ttgttagcgg           ttctcgagat               1441   gccactctta gggtttggga tattgagaca ggccagtgtt tacatgtttt           gatgggtcat               1501   gttgcagcag tccgctgtgt tcaatatgat ggcaggaggg ttgttagtgg           agcatatgat               1561   tttatggtaa aggtgtggga tccagagact gaaacctgtc tacacacgtt           gcaggggcat               1621   actaatagag tctattcatt acagtttgat ggtatccatg tggtgagtgg           atctcttgat               1681   acatcaatcc gtgtttggga tgtggagaca gggaattgca ttcacacgtt           aacagggcac               1741   cagtcgttaa caagtggaat ggaactcaaa gacaatattc ttgtctctgg           gaatgcagat               1801   tctacagtta aaatctggga tatcaaaaca ggacagtgtt tacaaacatt           gcaaggtccc               1861   aacaagcatc agagtgctgt gacctgttta cagttcaaca agaactttgt           aattaccagc               1921   tcagatgatg gaactgtaaa actatgggac ttgaaaacgg gtgaatttat           tcgaaaccta               1981   gtcacattgg agagtggggg gagtggggga gttgtgtggc ggatcagagc           ctcaaacaca               2041   aagctggtgt gtgcagttgg gagtcggaat gggactgaag aaaccaagct           gctggtgctg               2101   gactttgatg tggacatgaa gtga            
FBXW7 Protein ( Homo sapiens )
 
         [0000]    
       
         
               
               
             
               
               
               
             
           
               
                 SEQ ID NO: 68 
                   
               
             
          
           
               
                 1 
                 mnqellsvgs krrrtggslr gnpsssqvde eqmnrvveee qqqqlrqqee 
                   
               
               
                   
                 ehtarngevv 
               
               
                   
               
               
                 61 
                 gveprpggqn dsqqgqleen nnrfisvded ssgnqeeqee deehageqde 
               
               
                   
                 edeeeeemdq 
               
               
                   
               
               
                 121 
                 esddfdqsdd ssredehtht nsvtnsssiv dlpvhqlssp fytkttkmkr 
               
               
                   
                 kldhgsevrs 
               
               
                   
               
               
                 181 
                 fslgkkpckv seytsttglv pcsatpttfg dlraangqgq qrrritsvqp 
               
               
                   
                 ptglqewlkm 
               
               
                   
               
               
                 241 
                 fqswsgpekl laldelidsc eptqvkhmmq viepqfqrdf isllpkelal 
               
               
                   
                 yvlsflepkd 
               
               
                   
               
               
                 301 
                 llqaaqtcry wrilaednll wrekckeegi deplhikrrk vikpgfihsp 
               
               
                   
                 wksayirqhr 
               
               
                   
               
               
                 361 
                 idtnwrrgel kspkvlkghd dhvitclqfc gnrivsgsdd ntlkvwsavt 
               
               
                   
                 gkclrtlvgh 
               
               
                   
               
               
                 421 
                 tggvwssqmr dniiisgstd rtlkvwnaet gecihtlygh tstvrcmhlh 
               
               
                   
                 ekrvvsgsrd 
               
               
                   
               
               
                 481 
                 atlrvwdiet gqclhvlmgh vaavrcvqyd grrvvsgayd fmvkvwdpet 
               
               
                   
                 etclhtlqgh 
               
               
                   
               
               
                 541 
                 tnrvyslqfd gihvvsgsld tsirvwdvet gncihtltgh qsltsgmelk 
               
               
                   
                 dnilvsgnad 
               
               
                   
               
               
                 601 
                 stvkiwdikt gqclqtlqgp nkhqsavtcl qfnknfvits sddgtvklwd 
               
               
                   
                 lktgefirnl 
               
               
                   
               
               
                 661 
                 vtlesggsgg vvwrirasnt klvcavgsrn gteetkllvl dfdvdmk 
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
             
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
             
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 1 
               
             
             
               
                   
               
               
                 MCR overlap between murine TKO and human T-ALL datasets 
               
             
          
           
               
                   
                 Mouse 
                 Cancer 
                   
               
               
                   
                 TKO 
                 Genes 
                 Human T-ALL 
               
             
          
           
               
                   
                   
                   
                   
                   
                 Peak 
                   
                 or 
                   
                   
                   
                   
                 Peak 
               
               
                 MCR # 
                 Cytoband 
                 Start 
                 End 
                 Size (bp) 
                 Ratio 
                 Rec 
                 Candidates 
                 Chr 
                 Start 
                 End 
                 Size (bp) 
                 Ratio 
               
               
                   
               
             
          
           
               
                 Amplified MCRs 
               
             
          
           
               
                 1 
                 4E2 
                 153362787 
                 154677539 
                 1,314,752 
                 0.88 
                 13 
                 Dvl1; Ccnl2; 
                 1 
                 1286939.5 
                 1536335.5 
                 249,396 
                 1.11 
               
               
                   
                   
                   
                   
                   
                   
                   
                 Aurkaip1 
               
               
                 2 
                 10A3 
                 18124375 
                 22105516 
                 3,981,141 
                 1.91 
                 11 
                 Myb; Ahi1 
                 6 
                 135471648.5 
                 135829074.5 
                 357,426 
                 1.07 
               
               
                 3 
                 16C4 
                 91250715 
                 97408345 
                 6,157,630 
                 1.38 
                 21 
                 Runx1; Ets2; 
                 21 
                 40837575.5 
                 42285661.5 
                 1,448.086 
                 0.95 
               
               
                   
                   
                   
                   
                   
                   
                   
                 Tmprss2; 
               
               
                   
                   
                   
                   
                   
                   
                   
                 Ripk4; Erg 
               
               
                 4 
                 5G2 
                 136128574 
                 138413308 
                 2,284,734 
                 0.87 
                 14 
                 Gnb2; Perq1 
                 7 
                 99901102.5 
                 99949527 
                 48,425 
                 1.09 
               
               
                 5 
                 4A1 
                 5601642 
                 13568807 
                 7,967,165 
                 1.00 
                 11 
                 Tox 
                 8 
                 59880732.5 
                 60101149.5 
                 220,417 
                 0.82 
               
               
                 6 
                 2B 
                 29315580 
                 31992174 
                 2,676,594 
                 1.78 
                 7 
                 Set; Fnbp1; 
                 9 
                 130710910.5 
                 131134550.5 
                 423,640 
                 2.06 
               
               
                   
                   
                   
                   
                   
                   
                   
                 Abl1; 
               
               
                   
                   
                   
                   
                   
                   
                   
                 NUP214 
               
             
          
           
               
                 Deleted MCRs 
               
             
          
           
               
                 7 
                 11B3-B4 
                 68759068 
                 72041187 
                 3,282,119 
                 −0.93 
                 4 
                 Trp53; Bcl6b 
                 17 
                 6494426.5 
                 7767821.5 
                 1,273,395 
                 −0.76 
               
               
                 8 
                 3H4 
                 155474073 
                 158861389 
                 3,387,316 
                 −0.75 
                 3 
                 Negr1 
                 1 
                 71919083.5 
                 72444137.5 
                 525,054 
                 −0.92 
               
               
                 9 
                 15B3.1 
                 33212025 
                 41060793 
                 7,848,768 
                 −0.93 
                 2 
                 Baalc; Fzd6 
                 8 
                 104310865.5 
                 104499581.5 
                 188,716 
                 −0.93 
               
               
                 10 
                 16A1 
                 3264231 
                 10275117 
                 7,010,886 
                 −0.97 
                 21 
                 Crebbp; C2ta 
                 16 
                 3195168 
                 11549999.5 
                 8,354,832 
                 −1.09 
               
               
                 11 
                 19C3-D2 
                 46457272 
                 56116765 
                 9,659,493 
                 −0.77 
                 8 
                 Mxi1 
                 10 
                 111672720.5 
                 112043485.5 
                 370,765 
                 −0.90 
               
               
                 12 
                 4E2 
                 150778332 
                 154677539 
                 3,899,207 
                 −0.83 
                 2 
                 Hes3; 
                 1 
                 5983967.5 
                 6318619.5 
                 334,652 
                 −0.85 
               
               
                   
                   
                   
                   
                   
                   
                   
                 RPL22; 
               
               
                   
                   
                   
                   
                   
                   
                   
                 CHD5 
               
               
                 13 
                 11A1 
                 8844892 
                 12372703 
                 3,527,811 
                 −3.73 
                 14 
                 Ikaros 
                 7 
                 49539939.5 
                 50229252.5 
                 689,313 
                 −0.75 
               
               
                 14 
                 12F2 
                 111667310 
                 115272402 
                 3,605,092 
                 −1.43 
                 9 
                 Ptprn2 
                 7 
                 156125925.5 
                 158194699.5 
                 2,068,774 
                 −0.84 
               
               
                 15 
                 6B1 
                 41191601 
                 41690238 
                 498,637 
                 −5.48 
                 28 
                 TCRβ 
                 7 
                 141785426.5 
                 142078458.5 
                 293,032 
                 −3.07 
               
               
                 16 
                 19A 
                 11295986 
                 15610191 
                 4,314,205 
                 −0.77 
                 4 
                 Gnaq 
                 9 
                 77572992.5 
                 77916022.5 
                 343,030 
                 −0.76 
               
               
                 17 
                 19C1 
                 31573449 
                 32118682 
                 545,233 
                 −4.48 
                 13 
                 Pten 
                 10 
                 89594719.5 
                 90035234.5 
                 440,515 
                 −3.30 
               
               
                 18 
                 3E3-F1 
                 79297034 
                 87003791 
                 7,706,757 
                 −0.93 
                 2 
                 Fbxw7 
                 4 
                 153078068.5 
                 154979435.5 
                 1,901,367 
                 −1.74 
               
               
                   
               
               
                 Each murine TKO MCR with syntenic overlap with an MCR in the human T-ALL dataset is listed, separated by amplification and deletion, along with its chromosomal location (Cytoband/Chr) and base number (Start and End, in Mb). 
               
               
                 The minimal size of each MCR is indicated in bp. 
               
               
                 Peak ratio refers to the maximal log2 array-CGH ratio for each MCR. 
               
               
                 Rec refers to the number of tumors in which the MCR was defined. 
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
               
               
               
               
             
               
               
               
               
               
             
               
               
             
               
               
               
               
               
               
             
               
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 2 
               
             
             
               
                   
               
               
                 Summary of mutations in human T-ALL cell lines and primary 
               
               
                 samples 
               
               
                 Each case has been characterized for mutations in NOTCH1, FBXW7 
               
               
                 and PTEN. The table shows the breakdown of cell lines and primary 
               
               
                 T-ALL samples by two pairwise comparisons NOTCH1 × FBXW7 
               
               
                 and NOTCH1 × PTEN. Thus each case appears twice in the table, 
               
               
                 once in the FBXW7 column and once in the PTEN column. 
               
             
          
           
               
                   
                 FBXW7 
                   
               
             
          
           
               
                   
                   
                 Mut&#39;d/ 
                 PTEN 
               
             
          
           
               
                   
                 Wildtype 
                 Del&#39;d* 
                 Wildtype 
                 Mutated 
               
               
                   
                   
               
             
          
           
               
                 Cell lines 
                   
               
             
          
           
               
                 NOTCH1 
                 Wildtype 
                 5 
                 3 
                 7 
                 1 
               
               
                   
                 HD only 
                 1 
                 6 
                 4 
                 3 
               
               
                   
                 PEST only 
                 3 
                 1 
                 3 
                 1 
               
               
                   
                 HD + PEST 
                 3 
                 1 
                 2 
                 2 
               
             
          
           
               
                 Primary Samples 
                   
               
             
          
           
               
                 NOTCH1 
                 Wildtype 
                 12 
                 2 
                 12 
                 2 
               
               
                   
                 HD only 
                 6 
                 7 
                 13 
                 0 
               
               
                   
                 PEST only 
                 2 
                 1 
                 3 
                 0 
               
               
                   
                 HD + PEST 
                 7 
                 1 
                 8 
                 0 
               
               
                   
               
               
                 *mutated or deleted 
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 3 
               
             
             
               
                   
               
               
                 Murine TKO tumors used in this study. 
               
             
          
           
               
                   
                 Genotype 
                   
                 Characterization 
               
             
          
           
               
                 TUMOR 
                 mTerc 
                 Atm 
                 p53 
                 Surface marker phenotype 
                 aCGH 
                 SKY 
                 Notch1 Status 
               
               
                   
               
               
                 A701 
                 WT 
                 null 
                 het 
                 nd 
                 yes 
                 yes 
                   
               
               
                 KM343 
                 WT 
                 null 
                 het 
                 CD4+/− CD8+ 
                 yes 
                 yes 
               
               
                 CA342 
                 WT 
                 null 
                 het 
                 mixed CD4+ CD8+ and CD4− 
                 yes 
                 yes 
                 ins CC after 6961A 
               
               
                   
                   
                   
                   
                 CD8+ 
               
               
                 A494 
                 G0 
                 null 
                 WT 
                 CD4+ CD8+ 
                 yes 
                 yes 
                 ex34 deletion 
               
               
                 A934 
                 G0 
                 null 
                 ? 
                 nd 
                 yes 
                 yes 
               
               
                 A1005 
                 G0 
                 null 
                 het 
                 CD4− CD8+ 
                 yes 
                 yes 
                 aa1685 S to C 
               
               
                 A1252 
                 G0 
                 null 
                 het 
                 CD4− CD8+ 
                 yes 
                 yes 
                 ampl/trans? 
               
               
                 CA373 
                 G0 
                 null 
                 ? 
                 nd 
                 yes 
                 yes 
               
               
                 CA325 
                 G0 
                 null 
                 WT 
                 CD4+ CD8+/− 
                 yes 
                 yes 
                 del6848-6850CTA, ins 
               
               
                   
                   
                   
                   
                   
                   
                   
                 GGGG 
               
               
                 CA318 
                 G0 
                 null 
                 ? 
                 nd 
                 yes 
                 no 
                 del 7094A, insCCCCC 
               
               
                 CA290 
                 G0 
                 null 
                 het 
                 CD4− CD8+ 
                 yes 
                 yes 
                 del 7082G, insAA 
               
               
                 CA235 
                 G0 
                 null 
                 het 
                 nd 
                 yes 
                 no 
               
               
                 CA250 
                 G0 
                 null 
                 het 
                 nd 
                 yes 
                 no 
               
               
                 CA371 
                 G0 
                 null 
                 het 
                 nd 
                 yes 
                 no 
               
               
                 A1118 
                 G1 
                 null 
                 het 
                 nd 
                 yes 
                 no 
                 aa1685 S to C 
               
               
                 A725 
                 G1 
                 null 
                 WT 
                 CD4+ CD8+ 
                 yes 
                 yes 
                 del @ nt7260 
               
               
                 A933 
                 G1 
                 null 
                 het 
                 CD4− CD8+ 
                 yes 
                 no 
               
               
                 A1040 
                 G2 
                 null 
                 het 
                 CD4− CD8+ 
                 yes 
                 no 
               
               
                 A1240 
                 G2 
                 null 
                 het 
                 CD4− CD8− 
                 yes 
                 yes 
                 aa1685 S to C 
               
               
                 A689 
                 G4 
                 null 
                 het 
                 CD4+ CD8+ 
                 yes 
                 no 
                 del nt7219-7593 of ORF 
               
               
                 A785 
                 G3 
                 null 
                 WT 
                 CD4+ CD8+ 
                 yes 
                 no 
               
               
                 A570 
                 G3 
                 null 
                 het 
                 nd 
                 yes 
                 no 
               
               
                 A764 
                 G4 
                 null 
                 het 
                 nd 
                 yes 
                 no 
               
               
                 A543 
                 G4 
                 null 
                 het 
                 nd 
                 yes 
                 no 
               
               
                 A577 
                 G4 
                 null 
                 het 
                 CD4+ CD8+ 
                 yes 
                 yes 
                 ampl/trans? 
               
               
                 A897 
                 G4 
                 null 
                 null 
                 nd 
                 yes 
                 no 
               
               
                 A878 
                 G3 
                 null 
                 het 
                 Mixed CD4− CD8+ and CD4+ 
                 yes 
                 yes 
                 del @ nt7461 
               
               
                   
                   
                   
                   
                 CD8+ 
               
               
                 A791 
                 G3 
                 null 
                 het 
                 nd 
                 yes 
                 yes 
                 del @ nt7083 
               
               
                 A1060 
                 G3 
                 null 
                 het 
                 Mixed CD4+ CD8− and CD4+ 
                 yes 
                 yes 
                 aa1683 F to S 
               
               
                   
                   
                   
                   
                 CD8+ 
               
               
                 A895 
                 G4 
                 null 
                 null 
                 CD4+CD8+ 
                 yes 
                 yes 
                 ampl/trans? 
               
               
                 A684 
                 G4 
                 null 
                 het 
                 nd 
                 yes 
                 yes 
               
               
                 A1052 
                 G3 
                 null 
                 WT 
                 nd 
                 yes 
                 yes 
                 ampl/trans? 
               
               
                 CA456 
                 G0 
                 WT 
                 null 
                 CD4+/− CD8+ 
                 yes 
                 no 
                 amplification 
               
               
                 CA427 
                 G0 
                 het 
                 null 
                 CD4+/− CD8+ 
                 yes 
                 no 
                 amplification 
               
               
                 KM168 
                 G0 
                 WT 
                 null 
                 nd 
                 yes 
                 no 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 4A 
               
             
             
               
                   
               
               
                 T-ALL cell lines 
               
             
          
           
               
                   
                   
                   
                   
                   
                 Array- 
               
               
                 Sample 
                 Type 
                 Age 
                 Sex 
                 Sequenced* 
                 CGH* 
               
               
                   
               
             
          
           
               
                 BE-13 
                 cell line 
                 4 
                 F 
                 yes 
                 yes 
               
               
                 CCRF- 
                 cell line 
                 4 
                 F 
                 yes 
                 yes 
               
               
                 CEM 
               
               
                 CML-T1 
                 cell line 
                 36 
                 F 
                 yes 
                 no 
               
               
                 CTV-1 
                 cell line 
                 40 
                 F 
                 yes 
                 no 
               
               
                 DND41 
                 cell line 
                 13 
                 M 
                 yes 
                 yes 
               
               
                 DU528 
                 cell line 
                 16 
                 M 
                 yes 
                 yes 
               
               
                 HBP-ALL 
                 cell line 
                 14 
                 M 
                 yes 
                 yes 
               
               
                 J-RT3-T3-5 
                 cell line 
                 14 
                 M 
                 yes 
                 no 
               
               
                 KARPAS- 
                 cell line 
                 2 
                 M 
                 yes 
                 no 
               
               
                 45 
               
               
                 KE-37 
                 cell line 
                 27 
                 M 
                 yes 
                 no 
               
               
                 KopTK1 
                 cell line 
                 pediatric 
                   
                 yes 
                 yes 
               
               
                 LOUCY 
                 cell line 
                 38 
                 F 
                 yes 
                 yes 
               
               
                 ML-2 
                 cell line 
                 26 
                 M 
                 yes 
                 no 
               
               
                 MOLT-13 
                 cell line 
                 2 
                 F 
                 yes 
                 yes 
               
               
                 MOLT-16 
                 cell line 
                 5 
                 F 
                 yes 
                 yes 
               
               
                 MOLT-4 
                 cell line 
                 19 
                 M 
                 yes 
                 yes 
               
               
                 P12- 
                 cell line 
                 7 
                 M 
                 yes 
                 no 
               
               
                 ICHIKAWA 
               
               
                 PF-382 
                 cell line 
                 6 
                 F 
                 yes 
                 yes 
               
               
                 RPMI- 
                 cell line 
                 16 
                 F 
                 yes 
                 yes 
               
               
                 8402 
               
               
                 SupT11 
                 cell line 
                 74 
                 M 
                 yes 
                 yes 
               
               
                 SupT13 
                 cell line 
                 pediatric 
                   
                 yes 
                 yes 
               
               
                 SupT7 
                 cell line 
                 pediatric 
                   
                 yes 
                 yes 
               
               
                 TALL-1 
                 cell line 
                 28 
                 M 
                 yes 
                 yes 
               
               
                 Jurkat 
                 cell line 
                 14 
                 M 
                 no 
                 yes 
               
               
                 ALL-SIL 
                 cell line 
                 17 
                 M 
                 no 
                 yes 
               
               
                   
               
               
                 *indicates whether samples were used for either aCGH and/or re-squencing efforts 
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                 TABLE 4B 
               
             
             
               
                   
               
               
                 T-ALL tumors profiled by array-CGH* 
               
             
          
           
               
                   
                 Sample 
                 Type 
                 Age 
                 Sex 
               
               
                   
                   
               
             
          
           
               
                   
                 XC018-PB 
                 clinical 
                 10 
                 M 
               
               
                   
                 TL037 
                 clinical 
                 11 
                 M 
               
               
                   
                 MD108 
                 clinical 
                 15 
                 F 
               
               
                   
                 CO155 
                 clinical 
                 15 
                 F 
               
               
                   
                 RS128 
                 clinical 
                 4 
                 F 
               
               
                   
                 MP496 
                 clinical 
                 13 
                 F 
               
               
                   
                 JB238-PB 
                 clinical 
                 4 
                 M 
               
               
                   
                 BN066- 
                 normal 
               
               
                   
                 D28 
                 remission 
               
               
                   
                   
               
               
                   
                 *Clinical samples profiled by aCGH; samples not subjected to re-sequencing 
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                 TABLE 4C 
               
             
             
               
                   
               
               
                 Clinical specimens Sequenced* 
               
             
          
           
               
                   
                 Sample 
                 Type 
                 Age 
                 Sex 
               
               
                   
                   
               
             
          
           
               
                   
                 PD2716a 
                 clinical 
                 17 
                 F 
               
               
                   
                 PD2717a 
                 clinical 
                 19 
                 M 
               
               
                   
                 PD2718a 
                 clinical 
                 16 
                 M 
               
               
                   
                 PD2719a 
                 clinical 
                 14 
                 M 
               
               
                   
                 PD2720a 
                 clinical 
                 9 
                 M 
               
               
                   
                 PD2721a 
                 clinical 
                 33 
                 M 
               
               
                   
                 PD2722a 
                 clinical 
                 26 
                 F 
               
               
                   
                 PD2724a 
                 clinical 
                 55 
                 M 
               
               
                   
                 PD2725a 
                 clinical 
                 46 
                 M 
               
               
                   
                 PD2726a 
                 clinical 
                 25 
                 M 
               
               
                   
                 PD2727a 
                 clinical 
                 39 
                 M 
               
               
                   
                 PD2728a 
                 clinical 
                 24 
                 M 
               
               
                   
                 PD2729a 
                 clinical 
                 42 
                 M 
               
               
                   
                 PD2730a 
                 clinical 
                 26 
                 F 
               
               
                   
                 PD2731a 
                 clinical 
                 19 
                 M 
               
               
                   
                 PD2732a 
                 clinical 
                 46 
                 F 
               
               
                   
                 PD2733a 
                 clinical 
                 21 
                 M 
               
               
                   
                 PD2734a 
                 clinical 
                 37 
                 F 
               
               
                   
                 PD2735a 
                 clinical 
                 27 
                 M 
               
               
                   
                 PD2736a 
                 clinical 
                 16 
                 M 
               
               
                   
                 PD2737a 
                 clinical 
                 36 
                 M 
               
               
                   
                 PD2738a 
                 clinical 
                 8 
                 M 
               
               
                   
                 PD2739a 
                 clinical 
                 31 
                 M 
               
               
                   
                 PD2740a 
                 clinical 
                 35 
                 M 
               
               
                   
                 PD2741a 
                 clinical 
                 37 
                 M 
               
               
                   
                 PD2742a 
                 clinical 
                 44 
                 M 
               
               
                   
                 PD2743a 
                 clinical 
                 2 
                 M 
               
               
                   
                 PD2744a 
                 clinical 
                 25 
                 M 
               
               
                   
                 PD2745a 
                 clinical 
                 39 
                 F 
               
               
                   
                 PD2746a 
                 clinical 
                 32 
                 M 
               
               
                   
                 PD2747a 
                 clinical 
                 32 
                 M 
               
               
                   
                 PD2748a 
                 clinical 
                 7 
                 M 
               
               
                   
                 PD2749a 
                 clinical 
                 19 
                 M 
               
               
                   
                 PD2750a 
                 clinical 
                 44 
                 M 
               
               
                   
                 PD2751a 
                 clinical 
                 17 
                 M 
               
               
                   
                 PD2752a 
                 clinical 
                 30 
                 M 
               
               
                   
                 PD2753a 
                 clinical 
                 15 
                 M 
               
               
                   
                 PD2754a 
                 clinical 
                 17 
                 M 
               
               
                   
                   
               
               
                   
                 *Clinical specimens used for re-sequencing; samples not profiled by aCGH 
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 5 
               
             
             
               
                   
               
               
                 List of 160 MCRs defined in TKO genomes 
               
             
          
           
               
                   
                 Position 
                 Cytobands 
                 Peak 
                   
               
             
          
           
               
                 mid 
                 chn 
                 start 
                 end 
                 start 
                 end 
                 Ratio 
                 Recurrence 
                 Width (bp) 
                 # of Genes 
               
               
                   
               
             
          
           
               
                 141 
                 1 
                 1.05E+08 
                 1.06E+08 
                 1qE2.1 
                 1qE2.1 
                 1.044 
                 9 
                 1,110,166 
                 5 
               
               
                 68 
                 1 
                 1.28E+08 
                 1.28E+08 
                 1qE3 
                 1qE3 
                 0.945 
                 10 
                 362,010 
                 5 
               
               
                 67 
                 1 
                 1.28E+08 
                 1.28E+08 
                 1qE3 
                 1qE3 
                 2.099 
                 13 
                 142,785 
                 4 
               
               
                 70 
                 1 
                 1.31E+08 
                 1.36E+08 
                 1qE4 
                 1qE4 
                 0.888 
                 10 
                 5,086,790 
                 100 
               
               
                 69 
                 1 
                 1.36E+08 
                 1.39E+08 
                 1qE4 
                 1qE4 
                 0.888 
                 11 
                 2,430,212 
                 14 
               
               
                 149 
                 1 
                  1.5E+08 
                  1.5E+08 
                 1qG1 
                 1qG1 
                 1.041 
                 13 
                 31,937 
                 2 
               
               
                 86 
                 2 
                 18256403 
                 19011398 
                 2qA3 
                 2qA3 
                 1.552 
                 11 
                 754,995 
                 7 
               
               
                 85 
                 2 
                 26220146 
                 26426743 
                 2qA3 
                 2qA3 
                 2.521 
                 13 
                 206,597 
                 10 
               
               
                 87 
                 2 
                 29076116 
                 29113534 
                 2qB 
                 2qB 
                 0.946 
                 7 
                 37,418 
                 1 
               
               
                 88 
                 2 
                 29315580 
                 31992174 
                 2qB 
                 2qB 
                 1.782 
                 7 
                 2,676,594 
                 60 
               
               
                 89 
                 2 
                 32141443 
                 33152477 
                 2qB 
                 2qB 
                 1.258 
                 6 
                 1,011,034 
                 35 
               
               
                 5 
                 2 
                 86526803 
                 87088323 
                 2qD 
                 2qD 
                 0.937 
                 5 
                 561,520 
                 33 
               
               
                 105 
                 2 
                 1.29E+08 
                 1.31E+08 
                 2qF1 
                 2qF1 
                 1.191 
                 6 
                 2,182,234 
                 49 
               
               
                 73 
                 2 
                 1.49E+08 
                 1.57E+08 
                 2qG3 
                 2qH1 
                 0.907 
                 7 
                 8,124,884 
                 176 
               
               
                 72 
                 2 
                 1.57E+08 
                 1.58E+08 
                 2qH1 
                 2qH1 
                 0.898 
                 8 
                 89,827 
                 2 
               
               
                 42 
                 2 
                 1.78E+08 
                 1.78E+08 
                 2qH4 
                 2qH4 
                 1.043 
                 5 
                 56,696 
                 4 
               
               
                 45 
                 4 
                 5601642 
                 13568807 
                 4qA1 
                 4qA1 
                 1.001 
                 11 
                 7,967,165 
                 50 
               
               
                 48 
                 4 
                 43960797 
                 44207047 
                 4qB1 
                 4qB1 
                 0.855 
                 14 
                 246,250 
                 2 
               
               
                 49 
                 4 
                 46581252 
                 48074866 
                 4qB1 
                 4qB1 
                 0.966 
                 15 
                 1,493,614 
                 12 
               
               
                 46 
                 4 
                 59204015 
                 59696580 
                 4qB3 
                 4qB3 
                 1.312 
                 15 
                 492,565 
                 6 
               
               
                 47 
                 4 
                 61574346 
                 61615586 
                 4qB3 
                 4qB3 
                 1.759 
                 16 
                 41,240 
                 4 
               
               
                 50 
                 4 
                 67845996 
                 69605630 
                 4qC1 
                 4qC2 
                 0.962 
                 15 
                 1,759,634 
                 6 
               
               
                 107 
                 4 
                 73573051 
                 82835399 
                 4qC3 
                 4qC3 
                 0.844 
                 15 
                 9,262,348 
                 24 
               
               
                 8 
                 4 
                 1.06E+08 
                 1.06E+08 
                 4qC7 
                 4qC7 
                 0.928 
                 16 
                 121,051 
                 4 
               
               
                 6 
                 4 
                 1.47E+08 
                 1.51E+08 
                 4qE2 
                 4qE2 
                 0.821 
                 15 
                 4,128,560 
                 67 
               
               
                 7 
                 4 
                 1.53E+08 
                 1.55E+08 
                 4qE2 
                 4qE2 
                 0.881 
                 13 
                 1,314,752 
                 53 
               
               
                 118 
                 5 
                 29600288 
                 31438940 
                 5qB1 
                 5qB1 
                 0.882 
                 11 
                 1,838,652 
                 30 
               
               
                 75 
                 5 
                 44135455 
                 44256743 
                 5qB3 
                 5qB3 
                 1.188 
                 12 
                 121,288 
                 2 
               
               
                 9 
                 5 
                 85392518 
                 85451062 
                 5qE1 
                 5qE1 
                 0.882 
                 11 
                 58,544 
                 2 
               
               
                 14 
                 5 
                 1.02E+08 
                 1.02E+08 
                 5qE5 
                 5qE5 
                 0.841 
                 9 
                 185,602 
                 3 
               
               
                 12 
                 5 
                 1.05E+08 
                 1.08E+08 
                 5qE5 
                 5qF 
                 1.956 
                 10 
                 2,704,253 
                 33 
               
               
                 15 
                 5 
                 1.13E+08 
                 1.15E+08 
                 5qF 
                 5qF 
                 0.839 
                 12 
                 2,276,889 
                 54 
               
               
                 11 
                 5 
                 1.35E+08 
                 1.36E+08 
                 5qG2 
                 5qG2 
                 1.472 
                 13 
                 905,844 
                 15 
               
               
                 13 
                 5 
                 1.36E+08 
                 1.38E+08 
                 5qG2 
                 5qG2 
                 0.867 
                 14 
                 2,284,734 
                 75 
               
               
                 10 
                 5 
                 1.48E+08 
                  1.5E+08 
                 5qG3 
                 5qG3 
                 0.958 
                 15 
                 1,707,628 
                 22 
               
               
                 120 
                 6 
                 98525054 
                 1.03E+08 
                 6qD3 
                 6qD3 
                 1.417 
                 1 
                 4,114,423 
                 14 
               
               
                 121 
                 8 
                 30677625 
                 34627880 
                 8qA3 
                 8qA4 
                 0.752 
                 6 
                 3,950,255 
                 31 
               
               
                 111 
                 8 
                 74189294 
                 74204190 
                 8qC1 
                 8qC1 
                 0.895 
                 5 
                 14,896 
                 2 
               
               
                 17 
                 9 
                 29333867 
                 32712352 
                 9qA4 
                 9qA4 
                 1.776 
                 12 
                 3,378,485 
                 21 
               
               
                 20 
                 9 
                 44813433 
                 45348832 
                 9qA5.2 
                 9qA5.2 
                 0.850 
                 7 
                 535,399 
                 15 
               
               
                 16 
                 9 
                 46329619 
                 47484838 
                 9qA5.3 
                 9qA5.3 
                 1.555 
                 15 
                 1,155,219 
                 5 
               
               
                 123 
                 9 
                 53345703 
                 54059125 
                 9qA5.3 
                 9qA5.3 
                 0.752 
                 4 
                 713,422 
                 14 
               
               
                 124 
                 9 
                 56482435 
                 56638553 
                 9qB 
                 9qB 
                 0.887 
                 5 
                 156,118 
                 2 
               
               
                 125 
                 9 
                 59310802 
                 59590013 
                 9qB 
                 9qB 
                 0.752 
                 5 
                 279,211 
                 3 
               
               
                 76 
                 10 
                 18124375 
                 22105516 
                 10qA3 
                 10qA3 
                 1.914 
                 11 
                 3,981,141 
                 37 
               
               
                 77 
                 10 
                 39797713 
                 39991041 
                 10qB1 
                 10qB1 
                 0.933 
                 10 
                 193,328 
                 4 
               
               
                 114 
                 10 
                 75079313 
                 75286215 
                 10qC1 
                 10qC1 
                 0.918 
                 5 
                 206,902 
                 5 
               
               
                 127 
                 10 
                 93180073 
                 99904446 
                 10qC2 
                 10qD1 
                 0.854 
                 5 
                 6,724,373 
                 56 
               
               
                 104 
                 10 
                 1.27E+08 
                 1.27E+08 
                 10qD3 
                 10qD3 
                 0.854 
                 11 
                 299,603 
                 18 
               
               
                 143 
                 11 
                 3094931 
                 4168597 
                 11qA1 
                 11qA1 
                 0.757 
                 2 
                 1,073,666 
                 33 
               
               
                 100 
                 11 
                 32195496 
                 36843135 
                 11qA4 
                 11qA5 
                 0.872 
                 7 
                 4,647,639 
                 29 
               
               
                 101 
                 11 
                 40488257 
                 44855717 
                 11qA5 
                 11qB1.1 
                 0.898 
                 6 
                 4,367,460 
                 23 
               
               
                 102 
                 11 
                 45787203 
                 48749988 
                 11qB1.1 
                 11qB1.2 
                 0.932 
                 7 
                 2,962,785 
                 32 
               
               
                 128 
                 11 
                 1.17E+08 
                 1.18E+08 
                 11qE2 
                 11qE2 
                 0.755 
                 7 
                 822,168 
                 21 
               
               
                 129 
                 11 
                 1.18E+08 
                 1.19E+08 
                 11qE2 
                 11qE2 
                 0.808 
                 8 
                 726,438 
                 14 
               
               
                 78 
                 12 
                 38086004 
                 46238385 
                 12qB1 
                 12qB3 
                 0.981 
                 11 
                 8,152,381 
                 20 
               
               
                 79 
                 12 
                 47390537 
                 52540991 
                 12qB3 
                 12qC1 
                 1.466 
                 10 
                 5,150,454 
                 44 
               
               
                 80 
                 12 
                 55790095 
                 55837560 
                 12qC1 
                 12qC1 
                 0.942 
                 11 
                 47,465 
                 5 
               
               
                 51 
                 12 
                 75416967 
                 76481214 
                 12qC3 
                 12qC3 
                 0.828 
                 11 
                 1,064,247 
                 17 
               
               
                 53 
                 13 
                 3825590 
                 10409879 
                 13qA1 
                 13qA1 
                 1.243 
                 3 
                 6,584,289 
                 34 
               
               
                 54 
                 13 
                 23330778 
                 24380522 
                 13qA3.1 
                 13qA3.1 
                 1.039 
                 1 
                 1,049,744 
                 17 
               
               
                 56 
                 13 
                 46322053 
                 47532316 
                 13qA5 
                 13qA5 
                 0.976 
                 1 
                 1,210,263 
                 10 
               
               
                 25 
                 13 
                 99644459 
                 1.01E+08 
                 13qD1 
                 13qD1 
                 1.195 
                 2 
                 1,193,251 
                 13 
               
               
                 26 
                 13 
                 1.03E+08 
                  1.1E+08 
                 13qD2.1 
                 13qD2.2 
                 1.811 
                 2 
                 6,946,446 
                 47 
               
               
                 57 
                 14 
                 40458276 
                 41162221 
                 14qB 
                 14qB 
                 2.846 
                 25 
                 703,945 
                 9 
               
               
                 58 
                 14 
                 41747861 
                 44316485 
                 14qC1 
                 14qC1 
                 2.997 
                 24 
                 2,568,624 
                 30 
               
               
                 59 
                 14 
                 46887800 
                 48318364 
                 14qC1 
                 14qC1 
                 1.980 
                 22 
                 1,430,564 
                 63 
               
               
                 62 
                 14 
                 61322898 
                 67876948 
                 14qD1 
                 14qD2 
                 0.957 
                 15 
                 6,554,050 
                 72 
               
               
                 60 
                 14 
                 73311656 
                 73991889 
                 14qD3 
                 14qD3 
                 1.042 
                 14 
                 680,233 
                 11 
               
               
                 61 
                 14 
                 81055230 
                 81965738 
                 14qE1 
                 14qE1 
                 2.163 
                 14 
                 910,508 
                 2 
               
               
                 64 
                 14 
                 90605302 
                 91070049 
                 14qE2.1 
                 14qE2.1 
                 2.038 
                 14 
                 464,747 
                 1 
               
               
                 65 
                 14 
                 92428111 
                 93598116 
                 14qE2.1 
                 14qE2.1 
                 1.919 
                 14 
                 1,170,005 
                 5 
               
               
                 66 
                 14 
                 94810852 
                 97523812 
                 14qE2.2 
                 14qE2.3 
                 1.526 
                 14 
                 2,712,960 
                 10 
               
               
                 63 
                 14 
                 1.16E+08 
                 1.17E+08 
                 14qE5 
                 14qE5 
                 0.982 
                 16 
                 966,790 
                 12 
               
               
                 28 
                 15 
                 4902782 
                 6271853 
                 15qA1 
                 15qA1 
                 1.578 
                 17 
                 1,369,071 
                 9 
               
               
                 30 
                 15 
                 23144859 
                 32967402 
                 15qA2 
                 15qB3.1 
                 1.233 
                 18 
                 9,822,543 
                 41 
               
               
                 29 
                 15 
                 54425386 
                 63790043 
                 15qD1 
                 15qD1 
                 1.498 
                 20 
                 9,364,657 
                 68 
               
               
                 27 
                 15 
                 95452330 
                 1.03E+08 
                 15qF1 
                 15qF3 
                 1.028 
                 20 
                 7,131,911 
                 192 
               
               
                 33 
                 16 
                 42899450 
                 43217357 
                 16qB4 
                 16qB4 
                 0.988 
                 12 
                 317,907 
                 5 
               
               
                 31 
                 16 
                 48142711 
                 55198270 
                 16qB5 
                 16qC1.1 
                 0.989 
                 13 
                 7,055,559 
                 27 
               
               
                 32 
                 16 
                 55961953 
                 56077653 
                 16qC1.1 
                 16qC1.1 
                 0.913 
                 13 
                 115,700 
                 4 
               
               
                 34 
                 16 
                 74969013 
                 76202427 
                 16qC3.1 
                 16qC3.1 
                 1.030 
                 16 
                 1,233,414 
                 4 
               
               
                 83 
                 16 
                 83801341 
                 84228153 
                 16qC3.3 
                 16qC3.3 
                 1.293 
                 18 
                 426,812 
                 7 
               
               
                 82 
                 16 
                 86584797 
                 87663238 
                 16qC3.3 
                 16qC3.3 
                 1.178 
                 18 
                 1,078,441 
                 11 
               
               
                 81 
                 16 
                 91250715 
                 97408345 
                 16qC4 
                 16qC4 
                 1.378 
                 21 
                 6,157,630 
                 53 
               
               
                 36 
                 17 
                 11029895 
                 11172149 
                 17qA1 
                 17qA1 
                 0.997 
                 5 
                 142,254 
                 2 
               
               
                 35 
                 17 
                 12996985 
                 13092851 
                 17qA1 
                 17qA1 
                 1.423 
                 9 
                 95,866 
                 6 
               
               
                 37 
                 17 
                 28187374 
                 28772915 
                 17qA3.3 
                 17qA3.3 
                 1.272 
                 14 
                 585,541 
                 4 
               
               
                 40 
                 17 
                 31307004 
                 32045121 
                 17qB1 
                 17qB1 
                 0.920 
                 6 
                 738,117 
                 46 
               
               
                 39 
                 17 
                 33888591 
                 33972790 
                 17qB1 
                 17qB1 
                 1.647 
                 6 
                 84,199 
                 2 
               
               
                 41 
                 17 
                 48468702 
                 54249820 
                 17qC 
                 17qC 
                 0.834 
                 4 
                 5,781,118 
                 65 
               
               
                 84 
                 18 
                 44249076 
                 44496478 
                 18qB3 
                 18qB3 
                 0.907 
                 3 
                 247,402 
                 6 
               
               
                 92 
                 19 
                 3307019 
                 4813998 
                 19qA 
                 19qA 
                 1.091 
                 3 
                 1,506,979 
                 64 
               
               
                 93 
                 19 
                 8172318 
                 9587961 
                 19qA 
                 19qA 
                 1.242 
                 4 
                 1,415,643 
                 23 
               
               
                 94 
                 19 
                 9746944 
                 12276560 
                 19qA 
                 19qA 
                 1.449 
                 4 
                 2,529,616 
                 107 
               
               
                 103 
                 19 
                 38219064 
                 38791620 
                 19qC3 
                 19qC3 
                 0.763 
                 3 
                 572,556 
                 7 
               
               
                 95 
                 19 
                 43353084 
                 43585182 
                 19qC3 
                 19qC3 
                 0.961 
                 2 
                 232,098 
                 5 
               
               
                 96 
                 19 
                 44700687 
                 44972460 
                 19qC3 
                 19qC3 
                 1.023 
                 2 
                 271,773 
                 3 
               
               
                 97 
                 19 
                 45365601 
                 46170449 
                 19qC3 
                 19qC3 
                 0.876 
                 2 
                 804,848 
                 20 
               
               
                 140 
                 19 
                 54723418 
                 54846569 
                 19qD2 
                 19qD2 
                 0.898 
                 2 
                 123,151 
                 5 
               
               
                 98 
                 19 
                 59483972 
                 60620320 
                 19qD3 
                 19qD3 
                 1.339 
                 3 
                 1,136,348 
                 13 
               
               
                 221 
                 1 
                 29038485 
                 29089894 
                 1qA5 
                 1qA5 
                 −1.092 
                 1 
                 51,409 
                 2 
               
               
                 193 
                 2 
                 26426743 
                 30018849 
                 2qA3 
                 2qB 
                 −0.884 
                 1 
                 3,592,106 
                 70 
               
               
                 209 
                 2 
                 33052450 
                 33773524 
                 2qB 
                 2qB 
                 −0.948 
                 3 
                 721,074 
                 9 
               
               
                 177 
                 2 
                 1.67E+08 
                 1.68E+08 
                 2qH3 
                 2qH3 
                 −1.072 
                 2 
                 694,349 
                 12 
               
               
                 194 
                 2 
                 1.69E+08 
                  1.7E+08 
                 2qH3 
                 2qH3 
                 −0.871 
                 2 
                 548,165 
                 3 
               
               
                 195 
                 2 
                 1.72E+08 
                 1.72E+08 
                 2qH3 
                 2qH3 
                 −0.786 
                 3 
                 64,794 
                 2 
               
               
                 196 
                 3 
                 53093840 
                 57750461 
                 3qC 
                 3qD 
                 −1.000 
                 3 
                 4,656,621 
                 39 
               
               
                 237 
                 3 
                 72799409 
                 73392410 
                 3qE3 
                 3qE3 
                 −0.841 
                 3 
                 593,001 
                 2 
               
               
                 191 
                 3 
                 78211040 
                 78797254 
                 3qE3 
                 3qE3 
                 −0.841 
                 5 
                 586,214 
                 4 
               
               
                 197 
                 3 
                 79297034 
                 87003791 
                 3qE3 
                 3qF1 
                 −0.932 
                 2 
                 7,706,757 
                 56 
               
               
                 186 
                 3 
                 1.55E+08 
                 1.59E+08 
                 3qH4 
                 3qH4 
                 −0.752 
                 3 
                 3,387,316 
                 13 
               
               
                 198 
                 4 
                 1.11E+08 
                 1.12E+08 
                 4qD1 
                 4qD1 
                 −0.921 
                 2 
                 654,234 
                 8 
               
               
                 212 
                 4 
                 1.37E+08 
                 1.37E+08 
                 4qD3 
                 4qD3 
                 −1.153 
                 3 
                 217,944 
                 2 
               
               
                 224 
                 4 
                 1.51E+08 
                 1.55E+08 
                 4qE2 
                 4qE2 
                 −0.834 
                 2 
                 3,899,207 
                 78 
               
               
                 150 
                 5 
                 21196088 
                 21737788 
                 5qA3 
                 5qA3 
                 −1.044 
                 2 
                 541,700 
                 1 
               
               
                 151 
                 6 
                 41191601 
                 41690238 
                 6qB1 
                 6qB1 
                 −5.480 
                 28 
                 498,637 
                 21 
               
               
                 235 
                 6 
                 73593839 
                 80776018 
                 6qC1 
                 6qC3 
                 −0.787 
                 3 
                 7,182,179 
                 20 
               
               
                 229 
                 7 
                 1.26E+08 
                 1.26E+08 
                 7qF3 
                 7qF3 
                 −1.048 
                 2 
                 106,584 
                 3 
               
               
                 225 
                 7 
                 1.37E+08 
                  1.4E+08 
                 7qF5 
                 7qF5 
                 −0.895 
                 3 
                 2,633,930 
                 38 
               
               
                 213 
                 8 
                 76735909 
                 76808515 
                 8qC1 
                 8qC1 
                 −0.881 
                 4 
                 72,606 
                 2 
               
               
                 201 
                 10 
                 3207257 
                 9357502 
                 10qA1 
                 10qA1 
                 −0.976 
                 1 
                 6,150,245 
                 38 
               
               
                 183 
                 11 
                 8844892 
                 12372703 
                 11qA1 
                 11qA1 
                 −3.730 
                 14 
                 3,527,811 
                 18 
               
               
                 184 
                 11 
                 16565410 
                 17157549 
                 11qA2 
                 11qA2 
                 −0.947 
                 7 
                 592,139 
                 11 
               
               
                 230 
                 11 
                 25513879 
                 33407529 
                 11qA3.2 
                 11qA4 
                 −0.916 
                 5 
                 7,893,650 
                 61 
               
               
                 226 
                 11 
                 44209892 
                 44304867 
                 11qB1.1 
                 11qB1.1 
                 −0.935 
                 5 
                 94,975 
                 2 
               
               
                 189 
                 11 
                 68759068 
                 72041187 
                 11qB3 
                 11qB4 
                 −0.932 
                 4 
                 3,282,119 
                 125 
               
               
                 218 
                 11 
                 92848956 
                 93404029 
                 11qD 
                 11qD 
                 −0.927 
                 3 
                 555,073 
                 2 
               
               
                 227 
                 12 
                 93606364 
                 93916807 
                 12qE 
                 12qE 
                 −0.870 
                 3 
                 310,443 
                 3 
               
               
                 154 
                 12 
                 96250531 
                 96496843 
                 12qE 
                 12qE 
                 −0.895 
                 5 
                 246,312 
                 4 
               
               
                 153 
                 12 
                 98783592 
                 1.04E+08 
                 12qE 
                 12qF1 
                 −1.602 
                 15 
                 5,234,816 
                 66 
               
               
                 155 
                 12 
                 1.12E+08 
                 1.15E+08 
                 12qF2 
                 12qF2 
                 −1.427 
                 9 
                 3,605,092 
                 25 
               
               
                 179 
                 13 
                 18627216 
                 18826113 
                 13qA2 
                 13qA2 
                 −3.237 
                 12 
                 198,897 
                 1 
               
               
                 180 
                 13 
                 37254725 
                 37524185 
                 13qA3.3 
                 13qA3.3 
                 −0.986 
                 9 
                 269,460 
                 3 
               
               
                 181 
                 13 
                 48176346 
                 50100290 
                 13qA5 
                 13qA5 
                 −1.190 
                 9 
                 1,923,944 
                 31 
               
               
                 156 
                 13 
                 97118503 
                 98856406 
                 13qD1 
                 13qD1 
                 −0.875 
                 8 
                 1,737,903 
                 2 
               
               
                 203 
                 13 
                 1.14E+08 
                 1.15E+08 
                 13qD2.3 
                 13qD2.3 
                 −0.913 
                 8 
                 405,653 
                 1 
               
               
                 157 
                 14 
                 24250524 
                 24460588 
                 14qA3 
                 14qA3 
                 −1.187 
                 6 
                 210,064 
                 6 
               
               
                 240 
                 14 
                 44277623 
                 45455380 
                 14qC1 
                 14qC1 
                 −0.833 
                 4 
                 1,177,757 
                 22 
               
               
                 214 
                 14 
                 46642257 
                 46906069 
                 14qC1 
                 14qC1 
                 −2.581 
                 7 
                 263,812 
                 7 
               
               
                 215 
                 14 
                 46983329 
                 47000386 
                 14qC1 
                 14qC1 
                 −0.874 
                 3 
                 17,057 
                 3 
               
               
                 158 
                 14 
                 47563191 
                 48727495 
                 14qC1 
                 14qC1 
                 −4.918 
                 20 
                 1,164,304 
                 41 
               
               
                 204 
                 14 
                 63792812 
                 64013139 
                 14qD1 
                 14qD1 
                 −1.202 
                 8 
                 220,327 
                 4 
               
               
                 234 
                 14 
                  1.1E+08 
                 1.19E+08 
                 14qE4 
                 14qE5 
                 −0.990 
                 3 
                 8,712,984 
                 54 
               
               
                 205 
                 15 
                 3059822 
                 10112117 
                 15qA1 
                 15qA1 
                 −0.999 
                 2 
                 7,052,295 
                 52 
               
               
                 206 
                 15 
                 33212025 
                 41060793 
                 15qB3.1 
                 15qB3.1 
                 −0.935 
                 2 
                 7,848,768 
                 59 
               
               
                 228 
                 15 
                 91904361 
                 93343014 
                 15qE3 
                 15qE3 
                 −0.997 
                 2 
                 1,438,653 
                 9 
               
               
                 159 
                 16 
                 3264231 
                 10275117 
                 16qA1 
                 16qA1 
                 −0.971 
                 21 
                 7,010,886 
                 74 
               
               
                 160 
                 16 
                 15680940 
                 16190296 
                 16qA2 
                 16qA2 
                 −0.779 
                 10 
                 509,356 
                 16 
               
               
                 161 
                 16 
                 17292404 
                 18721258 
                 16qA3 
                 16qA3 
                 −0.958 
                 11 
                 1,428,854 
                 35 
               
               
                 162 
                 16 
                 19589196 
                 21020820 
                 16qA3 
                 16qB1 
                 −0.892 
                 9 
                 1,431,624 
                 20 
               
               
                 208 
                 18 
                 11094974 
                 11165506 
                 18qA1 
                 18qA1 
                 −0.791 
                 3 
                 70,532 
                 2 
               
               
                 239 
                 19 
                 11295986 
                 15610191 
                 19qA 
                 19qA 
                 −0.773 
                 4 
                 4,314,205 
                 106 
               
               
                 164 
                 19 
                 26046566 
                 28527676 
                 19qC1 
                 19qC1 
                 −0.851 
                 7 
                 2,481,110 
                 21 
               
               
                 165 
                 19 
                 28881381 
                 29036087 
                 19qC1 
                 19qC1 
                 −0.851 
                 5 
                 154,706 
                 4 
               
               
                 163 
                 19 
                 31573449 
                 32118682 
                 19qC1 
                 19qC1 
                 −4.479 
                 13 
                 545,233 
                 8 
               
               
                 166 
                 19 
                 33295876 
                 35125747 
                 19qC1 
                 19qC2 
                 −3.887 
                 6 
                 1,829,871 
                 22 
               
               
                 187 
                 19 
                 36783412 
                 41421335 
                 19qC2 
                 19qC3 
                 −0.951 
                 6 
                 4,637,923 
                 62 
               
               
                 220 
                 19 
                 46457272 
                 56116765 
                 19qC3 
                 19qD2 
                 −0.768 
                 8 
                 9,659,493 
                 65 
               
               
                 185 
                 19 
                 59063578 
                 59662870 
                 19qD3 
                 19qD3 
                 −0.768 
                 9 
                 599,292 
                 3 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
           
               
                 TABLE 6 
               
             
             
               
                   
               
               
                 Mutations in human T-ALL cell lines and primary samples. 
               
             
          
           
               
                 Sample 
                 FBXW7 mutation 
                 NOTCH1 mutation 
                 PTEN mutation 
               
               
                   
               
               
                 BE-13 
                 Homozygous Deletion 
                 Hom c.4802T &gt; C p.L1601P 
                   
               
               
                 CCRF-CEM 
                 Het c.1393C &gt; T p.R465C 
                 Het c.4784insCGCGCCTTCCCCACAACAGCTCCTTCCACTTCCTGC 
               
               
                   
                   
                 p.R1595 &gt; PRLPHNSSSHFL 
               
               
                 CML-T1 
                 Het c.1394G &gt; A p.R465H 
               
               
                 CTV-1 
                 Het c.1513C &gt; T p.R505C 
                 Het c.7571C &gt; A p.S2524* 
               
               
                 DND41 
                   
                 Hom c.4781T &gt; C p.L1594P 
               
               
                 DU528 
                 Het c.1394G &gt; A p.R465H 
               
               
                 HBP-ALL 
                 Het c.1580A &gt; G p.D527G 
                 Het c.4724T &gt; C p.L1575P, Het c.7329insGGGCCGTGGACG 
               
               
                   
                   
                 p.D2443fs*39 
               
               
                 J-RT3-T3-5 
                 Het c.1513C &gt; T p.R505C 
                   
                 Het c.696_697 &gt; 
               
               
                   
                   
                   
                 GGCCCATGG p.R233fs*11 
               
               
                 KARPAS-45 
                 Het c.1513C &gt; T p.R505C 
                 Het c.5129T &gt; C p.L1710P 
                 Hom c.1000C &gt; T p.R334* 
               
               
                 KE-37 
                   
                 Het c.7378C &gt; T p.Q2460* 
               
               
                 KopTK1 
                   
                 Het c.4802T &gt; C p.L1601P, Het c.7544_7545delCT p.P2515fs*4 
               
               
                 LOUCY 
               
               
                 ML-2 
                   
                 Het c.7544_7545delCT p.P2515fs*4 
               
               
                 MOLT-13 
                 Het c.1394G &gt; A p.R465H 
                 Het c.5036T &gt; C p.L1679P 
               
               
                 MOLT-16 
               
               
                 MOLT-4 
                   
                 Het c.7544_7545delCT p.P2515fs*4 
                 Hom c.797delA p.K266fs*9 
               
               
                 P12- 
                 Hom c.1513C &gt; T p.R505C 
                 Het c.5165ins- 
                 Hom c.818G &gt; A p.W273* 
               
               
                   
                   
                 CCCGGTTGGGCAGCCTCAACATCCCCTACAAGATCGAGGCCG 
               
               
                 ICHIKAWA 
                   
                 p.V1722 &gt; ARWGSLNIPYLIEA 
               
               
                 PF-382 
                   
                 Het c.4724T &gt; C p.L1575P, Het c.7480insGCCTCTTAGCT p.P2494fs*3 
                 Hom Exon 5 + 2 ins GCCG p.? 
               
               
                 RPMI-8402 
                 Hom c.1394G &gt; 
                 Het c.4754insCCGTGGAGCTGATGCCGCCGGAGC 
                 Het c.477G &gt; T p.R159S, Het 
               
               
                   
                 A p.R465H 
                 p.Q1585 &gt; PVELMPPE 
                 c.702_703insCCCCCGGCCC 
               
               
                   
                   
                   
                 p.D235fs*10 
               
               
                 SupT11 
               
               
                 SupT13 
               
               
                 SupT7 
                   
                 Het c.4778insGGGTGC p.F1593 &gt; LGA, Het c.7285insGC p.H2429fs*8 
                 Het c.699_700insAAGG 
               
               
                   
                   
                   
                 p.E234fs*9 
               
               
                 TALL-1 
               
               
                 PD2716a 
               
               
                 PD2717a 
                   
                 Het c.4802T &gt; C p.L1601P, Het c.7472insAA p.Y2491fs*1 
               
               
                 PD2718a 
               
               
                 PD2719a 
                   
                 Het c.4757T &gt; C p.L1586P, Het c.7331insGGGCATC p.V2444fs*37 
               
               
                 PD2720a 
                 Het c.1513C &gt; T p.R505C 
                 Het c.7253C &gt; T p.P2418L 
               
               
                 PD2721a 
                   
                 Het c.5036T &gt; A p.L16797Q 
               
               
                 PD2722a 
                 Het c.1393C &gt; T p.R465C 
                 Het c.4781T &gt; C p.L1594P, Het c.7333C &gt; T p.Q2445* 
               
               
                 PD2724a 
                   
                 Het c.4781T &gt; C p.L1594P 
               
               
                 PD2725a 
                   
                 Het c.4780insTTCGATA p.L1594_R1595 &gt; FDR 
               
               
                 PD2726a 
               
               
                 PD2727a 
                 Het c.1436G &gt; T p.R479L 
                 Het c.4844insTGTGCCG p.Q1615_F1618 &gt; LCR 
               
               
                 PD2728a 
               
               
                 PD2729a 
                 Het c.1268G &gt; T p.G423V 
                 Het c.4751insGTACCCACCCTAAGG p.E1584insGTHPKE 
               
               
                 PD2730a 
                   
                   
                 Het c.697_698insCACGCTA 
               
               
                   
                   
                   
                 p.R233fs*3 
               
               
                 PD2731a 
               
               
                 PD2732a 
                 Het c.1393C &gt; T p.R465C 
                 Het c.4858_4859 &gt; CCAGGGT p.Y1620 &gt; PGS 
               
               
                 PD2733a 
                   
                 Het c.5164insCCCCCGGGCAGT p.V1722 &gt; PPGSL 
               
               
                 PD2734a 
                 Het. c.1436G &gt; A p.R479Q 
                 Het c.4802T &gt; C p.L1601P 
               
               
                 PD2735a 
                   
                 Het c.4757T &gt; C p.L1586P, Het c.7544_7545delCT p.P2515fs*4 
               
               
                 PD2736a 
               
               
                 PD2737a 
                 Het c.1393C &gt; T p.R465C 
                 Het c.4776_8delCTT 4776insGAC p.H1592Q F1593T 
               
               
                 PD2738a 
                   
                 Het c.7478insCCCTTGACAGGC p.V2495* 
               
               
                 PD2739a 
               
               
                 PD2740a 
                 Het c.1393C &gt; T p.R465C 
                 Het c.4852_4854delTTC p.F1618del 
               
               
                 PD2741a 
                   
                 Het c.4790T &gt; A p.L1597H 
               
               
                 PD2742a 
                   
                 Het c.5025insGGG p.S1675_I1676insG, 
               
               
                   
                   
                 Het c.7330insAGGAAAAG p.V2444fs*37 
               
               
                 PD2743a 
               
               
                 PD2744a 
                   
                 Het c.4724T &gt; C p.L1575P, Het c.4757T &gt; C p.L1586P, Het c.7390delG 
               
               
                   
                   
                 p.A2464fs*13 
               
               
                 PD2745a 
                   
                 Het c.4850T &gt; A p.I1617N, Het c.7305insGGGTG p.S2436fs*2 
               
               
                 PD2746a 
                 Het c.1393C &gt; T p.R465C 
                 Het c.4779insGTCGCC p.L1594 &gt; VA 
               
               
                 PD2747a 
                   
                 Het c.4771insCCA p.F1591 &gt; SI, Het c.7538C &gt; T p.P2513L 
               
               
                 PD2748a 
                   
                 Het c.7372insTAGGGGTTA p.L2458fs*1 
               
               
                 PD2749a 
               
               
                 PD2750a 
               
               
                 PD2751a 
               
               
                 PD2752a 
                 Het Exon 7 + 1G &gt; AA p.? 
               
               
                 PD2753a 
                   
                   
                 Het c.694 &gt; GGGAGG 
               
               
                   
                   
                   
                 p.R232fs*25 
               
               
                 PD2754a 
                 Het c.2001insG 
               
               
                   
                 p.S668fs*26 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
             
               
             
               
               
               
             
               
             
               
               
               
             
           
               
                 TABLE 7 
               
             
             
               
                   
               
               
                 List of known cancer genes mapped to syntenic MCRs in TKO tumors 
               
             
          
           
               
                 Gene 
                   
                 Gene 
               
               
                 Symbols 
                 Gene Symbols 
                 Name 
               
               
                   
               
             
          
           
               
                 Oncogenes 
               
             
          
           
               
                 Myc 
                 myelocytomatosis oncogene 
                 29 
               
               
                 Btg1 
                 B-cell translocation gene 1, anti-proliferative 
                 127 
               
               
                 Set 
                 SET translocation 
                 88 
               
               
                 Fnbp1 
                 formin binding protein 1 
                 88 
               
               
                 Abl1 
                 v-abl Abelson murine leukemia oncogene 1 
                 88 
               
               
                 Nup214 
                 nucleoporin 214 
                 88 
               
               
                 (BC039282) 
               
               
                 Notch1 
                 Notch gene homolog 1 
                 85 
               
               
                 Cdk4 
                 cyclin-dependent kinase 4 
                 104 
               
               
                 Ddit3 
                 DNA-damage inducible transcript 3 
                 104 
               
               
                 Bcr 
                 breakpoint cluster region homolog 
                 114 
               
               
                 Patz1 
                 POZ (BTB) and AT hook containing zinc finger 1 
                 143 
               
               
                 (Zfp278) 
               
               
                 Tpr 
                 translocated promoter region 
                 149 
               
               
                 Rpl22 
                 ribosomal protein L22 
                 6 
               
               
                 Nr4a3 
                 nuclear receptor subfamily 4, group A, member 3 
                 49 
               
               
                 Mll1(Mll) 
                 myeloid/lymphoid or mixed-lineage leukemia 1 
                 20 
               
               
                 Gphn 
                 gephyrin 
                 51 
               
               
                 Fli1 
                 Friend leukemia integration 1 
                 17 
               
             
          
           
               
                 Tumor Suppressors 
               
             
          
           
               
                 Crebbp 
                 CREB binding protein 
                 159 
               
               
                 Trp53 
                 transformation related protein 53 
                 189 
               
               
                 Pten 
                 phosphatase and tensin homolog 
                 163 
               
               
                 Fbxw7 
                 F-box and WD-40 domain protein 7, 
                 197 
               
               
                   
                 archipelago homolog ( Drosophila ) 
               
               
                 Npm1 
                 nucleophosmin 1 
                 230 
               
               
                 Fas 
                 Fas (TNF receptor superfamily member) 
                 166 
               
               
                 (Tnfrsf6) 
               
               
                 Tsc1 
                 tuberous sclerosis 1 
                 193 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 8 
               
             
             
               
                   
               
               
                 primers used for real-time PCR 
               
             
          
           
               
                   
                 alternative 
                   
                   
                   
               
               
                 primer 
                 name 
                 sequence 
                 COMMENT 
               
               
                   
               
               
                 D19MIT13A 
                   
                 TCTGGCACAAAGAGTTCGTG (SEQ ID NO: 69) 
                 PAPSS2 gene 
                   
               
               
                 D19MIT13B 
                   
                 CTTTTGCAGGAGCAGGTAGG (SEQ ID NO: 70) 
               
               
                   
               
               
                 RM120 
                 AW107648 
                 AACAGGATATGTTTCTTGGCG (SEQ ID NO: 71) 
                 ATAD1 
               
               
                 RM121 
                   
                 GGGTTATAGATTGCGGGAGA (SEQ ID NO: 72) 
               
               
                   
               
               
                 RM127 
                   
                 CAGCCGCTGCGAGGATTATCCGTCTTC (SEQ ID 
                 PTEN exon 1 
               
               
                   
                   
                 NO: 73) 
               
               
                 RM128 
                   
                 GCGGTCGCTGATGCCCCTCGCTCTG (SEQ ID 
               
               
                   
                   
                 NO: 74) 
               
               
                   
               
               
                 RM122 
                 PMC270016P1 
                 AAAAGTTCCCCTGCTGATGATTTGT (SEQ ID NO: 
                 Between PTEN exon 5&amp;6 
               
               
                   
                   
                 75) 
               
               
                 RM123 
                   
                 TGTTTTTGACCAATTAAAGTAGGCTGTG (SEQ ID 
               
               
                   
                   
                 NO: 76) 
               
               
                   
               
               
                 119211 FOR 
                   
                 TGCAGTATAGAGCGTGCAGA (SEQ ID NO: 77) 
                 PTEN EXON 8 
               
               
                 119211 REV 
                   
                 AGTATCGGTTGGCCTTGTCT (SEQ ID NO: 78) 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                 TABLE 9 
               
             
             
               
                   
               
               
                 NCBI accession and reference numbers for cancer genes or 
               
               
                 candidate cancer genes listed in Table 1 
               
             
          
           
               
                   
                 Murine mRNA NM 
                 Murine Entrez 
                 Human Gene 
               
               
                 Gene Name 
                 designation 
                 Gene ID 
                 ID 
               
               
                   
               
             
          
           
               
                 Mm Dvl1 
                 NM_010091 
                 13542 
                 1855 
               
               
                 ccnl2 
                 NM_207678 
                 56036 
                 81669 
               
               
                 aurkaip1 
                 NM_025338 
                 66077 
                 54998 
               
               
                 myb 
                 NM_010848 
                 17863 
                 4602 
               
               
                 ahi1 
                 NM_026203 
                 52906 
                 54806 
               
               
                 runx1 
                 NM_009821; 
                 12394 
                 861 
               
               
                   
                 NM_001111021; 
               
               
                   
                 NM_001111022; 
               
               
                   
                 NM_001111023 
               
               
                 ets2 
                 NM_011809 
                 23872 
                 2114 
               
               
                 tmprss2 
                 NM_015775 
                 50528 
                 7113 
               
               
                 ripk4 
                 NM_023663 
                 72388 
                 54101 
               
               
                 erg 
                 NM_133659 
                 13876 
                 2078 
               
               
                 gnb2 
                 NM_010312 
                 14693 
                 2783 
               
               
                 perq1 
                 NM_031408 
                 57330 
                 64599 
               
               
                 tox 
                 NM_145711 
                 252838 
                 9760 
               
               
                 set 
                 NM_023871 
                 56086 
                 6418 
               
               
                 fnbp1 
                 NM_001038700; 
                 14269 
                 23048 
               
               
                   
                 NM_019406 
               
               
                 abl1 
                 NM_001112703; 
                 11350 
                 25 
               
               
                   
                 NM_009594 
               
               
                 nup214 
                 NM_172268 
                 227720 
                 8021 
               
               
                 trp53 
                 NM_011640.3 
                 22059 
                 7157 
               
               
                 bcl6 
                 NM_009744 
                 12053 
                 604 
               
               
                 negr1 
                 NM_001039094; 
                 320840 
                 257194 
               
               
                   
                 NM_177274 
               
               
                 baalc 
                 NM_080640 
                 118452 
                 79870 
               
               
                 fzd6 
                 NM_008056 
                 14368 
                 8323 
               
               
                 crebbp 
                 NM_001025432 
                 12914 
                 1387 
               
               
                 c2ta 
                 NM_007575 
                 12265 
                 4261 
               
               
                 mxi1 
                 NM_010847; 
                 17859 
                 4601 
               
               
                   
                 NM_001008542; 
               
               
                   
                 NM_001008543 
               
               
                 hes3 
                 NM_008237 
                 15207 
                 390992 
               
               
                 rpl22 
                 NM_009079 
                 19934 
                 6146 
               
               
                 chd5 
                 NM_001081376 
                 269610 
                 26038 
               
               
                 ikaros 
                 NM_009578 
                 22778 
                 10320 
               
               
                 ptprn2 
                 NM_011215 
                 19276 
                 5799 
               
               
                 tcrb 
                   
                 21577 
                 6957 
               
               
                 gnaq 
                 NM_008139 
                 14682 
                 2776 
               
               
                 pten 
                 NM_008960 
                 19211 
                 5728 
               
               
                 fbxw7 
                 NM_080428 
                 50754 
                 55294