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(12) Patent Application Publication (10) Pub. No.: US 2005/0259483 A1 Nakamura Et Al

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(12) Patent Application Publication (10) Pub. No.: US 2005/0259483 A1 Nakamura Et Al US 2005O2594.83A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2005/0259483 A1 Nakamura et al. (43) Pub. Date: Nov. 24, 2005 (54) GENES AND POLYPEPTDES RELATING TO Related U.S. Application Data PROSTATE CANCERS (63) Continuation-in-part of application No. PCT/JP03/ 12073, filed on Sep. 22, 2003. (75) Inventors: Yusuke Nakamura, Yokohama-shi (JP); Toyomasa Katagiri, Shinagawa-ku (60) Provisional application No. 60/414,873, filed on Sep. (JP); Hidewaki Nakagawa, 30, 2002. Provisional application No. 60/555,810, Shinagawa-ku (JP); Shuichi Nakatsuru, filed on Mar. 23, 2004. Saitama-shi (JP) Publication Classification (51) Int. Cl." ....................................................... G11C 5/00 Correspondence Address: (52) U.S. Cl. ........................................................ 365/189.07 TOWNSEND AND TOWNSEND AND CREW, LLP (57) ABSTRACT TWO EMBARCADERO CENTER EIGHTH FLOOR Objective methods for detecting and diagnosing prostate SAN FRANCISCO, CA 94111-3834 (US) cancer (PRC) or prostatic intraepithelial neoplasia (PIN) are described herein. In one embodiment, the diagnostic method (73) Assignees: Oncotherapy Science, Inc., Kawasaki involves the determining an expression level of PRC-asso shi (JP); The University of Tokyo, Bun ciated gene that discriminate between PRC or PIN and kyo-ku (JP) nomal cell. The present invention further provides methods of Screening for therapeutic agents useful in the treatment of (21) Appl. No.: 11/088,634 either or both of PRC and PIN, methods of treating either or both of PRC and PIN and method of vaccinating a subject (22) Filed: Mar. 23, 2005 against either or both of PRC and PIN. Patient No. 313 bp 198bp 287 bp Patent Application Publication Nov. 24, 2005 Sheet 1 of 3 US 2005/0259483 A1 FIG.1 Patient No. Patent Application Publication Nov. 24, 2005 Sheet 2 of 3 US 2005/0259483 A1 FIG.2 (A) |d d|89 N H-o N N N N N H Z (B) 3 (kb) 9.5 7.5 4.4- 2.4 1 35 Patent Application Publication Nov. 24, 2005 Sheet 3 of 3 US 2005/0259483 A1 FIG.3 al (D . i (C) 0.04 US 2005/0259483 A1 Nov. 24, 2005 GENES AND POLYPEPTDES RELATING TO (1999)). However, the mechanism of PIN development and PROSTATE CANCERS the progression from PIN to PRC remain unclear. Therefore, genome-wide analysis of expression profiles in PINS is an CROSS-REFERENCES TO RELATED essential Step toward understanding the molecular carcino APPLICATIONS genesis and progression and the preventive Strategies of 0001. This application is a continuation-in-part of PCT/ PRC. JP2003/012073 (WO 2004/031414), which claims the ben 0006 cDNA microarray technologies have enabled to efit of U.S. Ser. No. 60/414,873, filed Sep. 30, 2002. This obtain comprehensive profiles of gene expression in normal application also claims the benefit of 60/555,810, filed Mar. and malignant cells, and compare the gene expression in 23, 2004. All of these applications are incorporated herein malignant and corresponding normal cells (Okabe et al., by reference. Cancer Res 61:2129-37 (2001); Kitahara et al., Cancer Res 61: 3544-9 (2001); Lin et al., Oncogene 21:4120-8 (2002); FIELD OF THE INVENTION Hasegawa et al., Cancer Res 62:7012-7 (2002)). This approach enables to disclose the complex nature of cancer 0002 This invention relates to methods of diagnosing cells, and helps to understand the mechanism of carcino and treating prostate cancer. In particular, the present inven genesis. Identification of genes that are deregulated in tion relates to novel polypeptides encoded by a novel gene tumors can lead to more precise and accurate diagnosis of B3537(CCDC4) relating to prostate cancer. Furthermore, individual cancers, and to develop novel therapeutic targets the present invention relates to the novel gene CCDC4. The (Bienz and Clevers, Cell 103:311-20 (2000)). To disclose genes and polypeptides of the present invention can be used, mechanisms underlying tumors from a genome-wide point for example, in the diagnosis of prostate cancer, as target of view, and discover target molecules for diagnosis and molecules for developing drugs against the disease, and for development of novel therapeutic drugs, the present inven attenuating cell growth of prostate cancer. tors have been analyzing the expression profiles of tumor cells using a cDNA microarray of 23040 genes (Okabe et al., BACKGROUND OF THE INVENTION Cancer Res 61:2129-37 (2001); Kitahara et al., Cancer Res 0003 Prostate cancer (PRC) is one of the most common 61:3544-9 (2001); Lin et al., Oncogene 21:4120-8 (2002); malignancies in men and represents a Significant Worldwide Hasegawa et al., Cancer Res 62:7012-7 (2002)). health problem. It is the Second most frequent cause of 0007 Studies designed to reveal mechanisms of carcino cancer death in the United States (Greenlee et al., CA Cancer genesis have already facilitated identification of molecular J Clin, 51:15-36 (2001)). Incidence of PRC is increasing targets for anti-tumor agents. For example, inhibitors of Steadily in developed countries according to the prevalence farnesyltransferase (FTIs) which were originally developed of Western-style diet and increasing number of Senior popu to inhibit the growth-signaling pathway related to Ras, lation. Increasing number of patients also die from this whose activation depends on posttranslational farnesylation, disease in Japan due to adoption of a Western life Style has been effective in treating Ras-dependent tumors in (Kuroishi, T., Klinika, 25:43-48 (1995)). Currently, the diag animal models (He et al., Cell 99:335-45 (1999)). Clinical nosis of PRC is based on an increased level of the serum trials on human using a combination or anti-cancer drugs prostate specific antigen (PSA). Early diagnosis provides an and anti-HER2 monoclonal antibody, trastuzumab, have opportunity for curative Surgery. Patients with organ con been conducted to antagonize the proto-oncogene receptor fined PRC are usually treated and approximately 70% of HER2/neu, and have been achieving improved clinical them are curable with radical prostatectomy (Roberts et al., response and overall Survival of breast-cancer patients (Lin Urology, 57:1033-1037 (2001); Roberts et al., Mayo Clin et al., Cancer Res 61:6345-9 (2001)). A tyrosine kinase Proc, 76:576-581 (2001)). Most of patients with advanced or inhibitor, STI-571, which selectively inactivates bcr-abl relapsed disease are treated with androgen ablation therapy fusion proteins, has been developed to treat chronic myel because growth of PRC is initially androgen dependent. ogenous leukemias wherein constitutive activation of bcr Although most of these patients initially respond to andro abl tyrosine kinase plays a crucial role in the transformation gen ablation therapy, the disease eventually progresses to of leukocytes. Agents of these kinds are designed to Suppress androgen-independent PRC, at which point the tumor is no oncogenic activity of specific gene products (Fujita et al., longer responsive to androgen ablation therapy. Cancer Res 61.7722-6 (2001)). Therefore, gene products 0004 One of the most serious clinical problems of treat commonly up-regulated in cancerous cells may serve as ment for PRC is that this androgen-independent PRC is potential targets for developing novel anti-cancer agents. unresponsive to any other therapies, and understanding the 0008. It has been demonstrated that CD8+ cytotoxic T mechanism of androgen-independent growth and establish lymphocytes (CTLs) recognize epitope peptides derived ing new therapies other than androgen ablation therapy from tumor-associated antigens (TAAS) presented on MHC against PRC are urgent issues for management of PRC. Class I molecule, and lyse tumor cells. Since the discovery 0005. On the other hand, prostatic intraepithelial neopla of MAGE family as the first example of TAAS, many other sia (PIN) is the specific type of minimal lesion that is TAAS have been discovered using immunological believed to be the precursor of PRC (McNeal, J. E. and approaches (Boon, Int J Cancer 54: 177-80 (1993); Boon Bostwick, D. G., Hum Pathol, 17, 64-71 (1986)). PIN is and van der Bruggen, J Exp Med 183: 725-9 (1996); van der regarded as a continuum between low-grade and high-grade Bruggen et al., Science 254: 1643-7 (1991); Brichard et al., forms, and high-grade PIN is considered to be the immediate J Exp Med 178: 489-95 (1993); Kawakami et al., J Exp Med precursor of invasive carcinoma. High-grade PIN and PRC 180: 347-52 (1994)). Some of the discovered TAAS are now frequently coexist and they share the Similar chromosomal in the Stage of clinical development as targets of immuno and genetic alterations (Qian et al., Eur Urol, 35, 479-83 therapy. TAAS discovered so far include MAGE (van der US 2005/0259483 A1 Nov. 24, 2005 Bruggen et al., Science 254: 1643-7 (1991)), gp100 that are differentially expressed in either or both of PRC and (Kawakami et al., J Exp Med 180: 347-52 (1994)), SART PIN are collectively referred to herein as “PRC nucleic (Shichijo et al., J Exp Med 187: 277-88 (1998)), and acids” or “PRC polynucleotides” and the corresponding NY-ESO-1 (Chen et al., Proc Natl AcadSci USA 94: 1914-8 encoded polypeptides are referred to as “PRC polypeptides’ (1997)). On the other hand, gene products which had been or “PRC proteins.” demonstrated to be specifically over-expressed in tumor 0012. Accordingly, the invention features a method of cells, have been shown to be recognized as targets inducing diagnosing or determining a predisposition to either or both cellular immune responses. Such gene products include p53 of PRC and PIN in a subject by determining an expression (Umano et al., Brit J Cancer 84: 1052-7 (2001)), HER2/neu. level of a PRC-associated gene in a patient derived biologi (Tanaka et al., Brit J Cancer 84:94-9 (2001)), CEA (Nukaya cal Sample, Such as tissue Sample.
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