中国人前列腺癌新融合基因的识别及其功能研究

项目名称： 中国人前列腺癌新融合基因的识别及其功能研究

项目编号： No.81472408

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 王建业

作者单位： 北京医院

项目金额： 70万元

中文摘要： 前列腺癌（PC）携带特异性融合基因，在多人群中得到证据。然在中国人群中并非多见，为此我们假设存有新的融合基因在中国人PC发生发展中起作用。本组前期通过人体标本的全转录组测序及生物信息学分析，经组织标本的RT-PCR和Sanger测序验证，识别了4个新的前列腺癌特异性融合基因。为深入验证该假设，本课题拟对其中2个融合基因进行深入探讨。首先通过RT-PCR、Long-PCR、FISH以及Mate-paired测序技术在扩大组织样本中，从mRNA和基因组水平检测新融合基因的发生频率和融合模式。其次在PC3细胞系，检测融合基因对肿瘤形成、细胞增殖、衰老、侵润及对雄激素和雄激素受体拮抗剂作用的影响。再次在免疫缺陷鼠中检测融合基因对肿瘤形成、转移及雄激素受体拮抗剂作用的影响，最后评价新融合基因与PC复发的关系。本研究从多个方面探讨新融合基因在PC中的作用，为寻找肿瘤标记物及其药物靶标提供线索。

中文关键词： 前列腺癌；融合基因；ETS

英文摘要： TMPRSS2:ERG gene fusion in prostate cancer (PC) have been reported in diverse populations, but it is not frequent in Chinese. Thus, we hypothesized that unknown genomic rearranged events are impacted in Chinese PC process. We adopted a whole transcriptome sequencing in 9 paired PC tissues and normal adjacent tissues that are not carry TMPRSS2:ERG gene fusion.We identified four unkown gene fusions.To futher test our hypothesis, we intend to study biological role of two of four fusion genes in PC process. Firstly,we are going to identify recurrence frequency and fuion patterns of two fusion gens in 177 Chinese PC sample set using RT-PCR、Long-PCR、FISH and Mate-paired sequencing.Next,we are going to test effects of these gene fusions on tumorigenosis、cell proliferation、cell senescence、invasion and response to androgen and antiandrogen in PC3 cell line.Subsequently, we are also going to test role of the two gene fusions on tumorigenosis and metastasis in immunodeficienct mice as well. Finally，we are going to assess the correlation between these gene fusions and recurrence of PC in 87 Chinese patients. Conclusion: This study aims to investigate potential roles of the two gene fusions in PC process and to provide insight into developing tumor markers and targeted therapy of PC.

英文关键词： prostate cancer;fusion gene;ETS