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Wo 2010/081001 A2 (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date 15 July 2010 (15.07.2010) WO 2010/081001 A2 (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every C12Q 1/68 (2006.01) kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, (21) International Application Number: CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, PCT/US20 10/020501 DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, (22) International Filing Date: HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, ! January 2010 (08.01 .2010) KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, (25) Filing Language: English NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, (26) Publication Language: English SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (30) Priority Data: 61/143,598 9 January 2009 (09.01 .2009) US (84) Designated States (unless otherwise indicated, for every 61/187,776 17 June 2009 (17.06.2009) US kind of regional protection available): ARIPO (BW, GH, GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, (71) Applicant (for all designated States except US): THE ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, REGENTS OF THE UNIVERSITY OF MICHIGAN TM), European (AT, BE, BG, CH, CY, CZ, DE, DK, EE, [US/US]; 1214 South University, 2nd Floor, Ann Arbor, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, Michigan 48104 (US). MC, MK, MT, NL, NO, PL, PT, RO, SE, SI, SK, SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, (72) Inventor; and ML, MR, NE, SN, TD, TG). (75) Inventor/Applicant (for US only): CHINNAIYAN, Arul, M. [US/US]; 51300 Plymouth Valley Drive, Ply Published: mouth, Michigan 48170 (US). — without international search report and to be republished (74) Agent: ARENSON, Tanya, A.; Casimir Jones, S.C., upon receipt of that report (Rule 48.2(g)) 2275 Deming Way, Suite 310, Middleton, Wisconsin 53562 (US). (54) Title: RECURRENT GENE FUSIONS IN CANCER (57) Abstract: The present invention relates to compositions and methods for cancer diagnosis, research and therapy, including but not limited to, cancer markers. In particular, the present invention relates to recurrent gene fusions as diagnostic markers and clinical targets for cancer (e.g., prostate cancer). RECURRENT GENE FUSIONS IN CANCER CROSS REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. provisional applications 61/143,598, filed January 9, 2009 and 61/187,776, filed June 17, 2009, each of which is herein incorporated by reference in its entirety. GOVERNMENT SUPPORT This invention was made with government support under grant numbers CA069568, CAl 11275 awarded by the National Institutes of Health and grant number W81XWH-08- 1-0031 awarded by the Army. The government has certain rights in the invention. FIELD OF THE INVENTION The present invention relates to compositions and methods for cancer diagnosis, research and therapy, including but not limited to, cancer markers. In particular, the present invention relates to recurrent gene fusions as diagnostic markers and clinical targets for cancer (e.g., prostate cancer). BACKGROUND OF THE INVENTION A central aim in cancer research is to identify altered genes that are causally implicated in oncogenesis. Several types of somatic mutations have been identified including base substitutions, insertions, deletions, translocations, and chromosomal gains and losses, all of which result in altered activity of an oncogene or tumor suppressor gene. First hypothesized in the early 1900's, there is now compelling evidence for a causal role for chromosomal rearrangements in cancer (Rowley, Nat Rev Cancer 1: 245 (2001)). Recurrent chromosomal aberrations were thought to be primarily characteristic of leukemias, lymphomas, and sarcomas. Epithelial tumors (carcinomas), which are much more common and contribute to a relatively large fraction of the morbidity and mortality associated with human cancer, comprise less than 1% of the known, disease-specific chromosomal rearrangements (Mitelman, Mutat Res 462: 247 (2000)). While hematological ma lignancies are often characterized by balanced, disease-specific chromosomal rearrangements, most solid tumors have a plethora of non-specific chromosomal aberrations. It is thought that the karyotypic complexity of solid tumors is due to secondary alterations acquired through cancer evolution or progression. Two primary mechanisms of chromosomal rearrangements have been described. In one mechanism, promoter/enhancer elements of one gene are rearranged adjacent to a proto-oncogene, thus causing altered expression of an oncogenic protein. This type of translocation is exemplified by the apposition of immunoglobulin (IG) and T-cell receptor (TCR) genes to MYC leading to activation of this oncogene in B- and T-cell malignancies, respectively (Rabbitts, Nature 372: 143 (1994)). In the second mechanism, rearrangement results in the fusion of two genes, which produces a fusion protein that may have a new function or altered activity. The prototypic example of this translocation is the BCR-ABL gene fusion in chronic myelogenous leukemia (CML) (Rowley, Nature 243: 290 (1973); de Klein et al, Nature 300: 765 (1982)). Importantly, this finding led to the rational development of imatinib mesylate (Gleevec), which successfully targets the BCR-ABL kinase (Deininger et al., Blood 105: 2640 (2005)). Thus, identifying recurrent gene rearrangements in common epithelial tumors may have profound implications for cancer drug discovery efforts as well as patient treatment. SUMMARY OF THE INVENTION The present invention relates to compositions and methods for cancer diagnosis, research and therapy, including but not limited to, cancer markers. In particular, the present invention relates to recurrent gene fusions as diagnostic markers and clinical targets for cancer (e.g., prostate cancer). For example, in some embodiments, the present invention provides a method for identifying prostate cancer in a patient comprising: providing a sample from the patient; and detecting the presence or absence in the sample of a gene fusion having a 5' portion from a transcriptional regulatory region of an SLC45A3 gene and a 3' portion from an ELK4 gene, wherein detecting the presence in the sample of the gene fusion identifies prostate cancer in the patient. In some embodiments, the transcriptional regulatory region of the SLC45A3 gene comprises a promoter region of the SLC45A3 gene. In some embodiments, the detecting comprises detecting chimeric mRNA transcripts having a 5' RNA portion transcribed from the transcriptional regulatory region of the SLC45A3 gene and a 3' RNA portion transcribed from the ELK4 gene. In some embodiments, the gene fusion is a read through transcript. In some embodiments, the sample is tissue, blood, plasma, serum, urine, urine supernatant, urine cell pellet, semen, prostatic secretions or prostate cells. In some embodiments, the method further comprises the step of detecting the presence or absence of a gene fusion having a 5' portion from a transcriptional regulatory region of an androgen regultated gene or a housekeeping gene and a 3' portion from an ETS family member gene. In other embodiments, the present invention provides a method for identifying prostate cancer in a patient comprising: providing a sample from the patient; and detecting the presence or absence in the sample of a gene fusion selected from USP10:ZDHHC7, EIF4E2:HJURP, HJURP:INPP4ASTRN4:GPSN2, RC3H2:RGS3, LMAN2:AP3S1, ZNF649-ZNF577 or MIPOLl :DGKB, wherein detecting the presence in the sample of the gene fusion is identifies prostate cancer in the patient. In some embodiments, the detecting comprises detecting chromosomal rearrangements of genomic DNA. In some embodiments, the detecting comprises detecting chimeric mRNA transcripts or read through transcripts. In some embodiments, the sample is tissue, blood, plasma, serum, urine, urine supernatant, urine cell pellet, semen, prostatic secretions or prostate cells. In further embodiments, the present invention provides a method for identifying prostate cancer in a patient comprising: providing a sample from the patient; and detecting the presence or absence in the sample of a gene fusion having a 5' portion from a transcriptional regulatory region of an HERPUDl gene and a 3' portion from an ERG gene, wherein detecting the presence in the sample of the gene fusion identifies prostate cancer in the patient. In yet other embodiments, the present invention provides a method for identifying prostate cancer in a patient comprising: providing a sample from the patient; and detecting the presence or absence in the sample of a gene fusion having a 5' portion from a transcriptional regulatory region of an AX747630 gene and a 3' portion from an ETVl gene, wherein detecting the presence in the sample of the gene fusion identifies prostate cancer in the patient. In additional embodiments, the present invention provides a method for identifying prostate cancer in a patient comprising: providing a sample from the patient; and detecting the presence or absence in the sample of a gene fusion selected from HERPUDl :ERG, TIAl :DIRC2, NUP214:XKR3, DLEU2:PSPC1, PIK3C2A:TEADl, SPOCKl :TBC1D9B, or RERE:PIK3CD, wherein detecting the presence in the sample of the gene fusion is identifies prostate cancer in the patient. Further embodiments of the present invention provide a method for identifying breast cancer in a patient comprising: providing a sample from the patient; and detecting the presence or absence in the sample of a gene fusion selected from AHCYL 1:RAD5 1C, ARHGAPl 9:DRG1, BCOl 7255 :TMEM49, FCHOl :MY09B, or PAPOLA:AK7, wherein detecting the presence in the sample of the gene fusion is identifies prostate cancer in the patient.
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