食管癌中NTRK3基因重排的鉴定及其作用机制研究

项目名称： 食管癌中NTRK3基因重排的鉴定及其作用机制研究

项目编号： No.81201593

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学1

项目作者： 郝佳洁

作者单位： 中国医学科学院肿瘤医院

项目金额： 23万元

中文摘要： 基因重排与肿瘤发生发展的关系愈来愈受到重视，我们在前期工作中发现食管癌细胞系KYSE450和KYSE510中存在NTRK3基因的断裂，并在KYSE450中鉴定出NTRK3基因形成了融合转录本。对临床食管癌组织标本进行FISH检测，发现16.7%的病例中存在NTRK3基因的断裂，提示NTRK3涉及的基因重排可能在食管癌中起重要作用。本研究拟在前期发现的基础上，选取存在NTRK3断裂的肿瘤组织样本，利用分子生物学和细胞生物学技术，针对NTRK3的断裂连接点进行序列分析，证实基因在断裂阳性病例中NTRK3基因的重排方式和蛋白表达情况，并扩大样本进行验证；继而利用细胞和动物模型，研究NTRK3基因重排对食管癌细胞恶性表型和裸鼠致瘤能力的影响；进一步分析NTRK3基因重排在食管癌中参与的信号通路及其影响的下游基因，揭示其在食管癌中发挥作用的分子机制。

中文关键词： 食管癌；NTRK3；基因重排；基因突变；功能研究

英文摘要： Chromosomal and gene rearrangements are common features of human malignant tumors. Chromosomal rearrangements may influence gene expression through several ways. First, fusion genes may be resulted from chromosomal translocations, inversions, and insertions, and thus expressing new fusion proteins with abnormal functions. Second, the regulatory elements are fused to the vicinity of normal genes, and dysregulate the gene expression. Third, gene truncations may be resulted from the gene breakage, and thus express the truncated proteins. All of the situations above might lead to the malignant transformations. The implications and the clinical values of gene rearrangements have been emphasized since years ago. Many fusion genes have been reported to play important roles in tumor development and progression, and several have been used for the assistant diagnosis as well as the targets for therapies. For a long period, the majority of gene rearrangements were discovered and in hematological malignancies. The findings for epithelial cancers were main reasons were the technical limitations and the complex karyotypes. Until recently, more and more fusion genes have been identified in multiple types of epithelial cancers, including prostate, lung, breast, colorectal, gastric, hepatoma carcinoma and so on. Esophageal squa

英文关键词： esophageal squamous cell carcinoma；NTRK3；gene rearrangement；gene mutation；function study