DNA甲基化调控非小细胞肺癌发生发展的作用机制

项目名称： DNA甲基化调控非小细胞肺癌发生发展的作用机制

项目编号： No.31200967

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 遗传学与生物信息学、细胞生物学

项目作者： 务勇圣

作者单位： 中国科学院北京基因组研究所

项目金额： 20万元

中文摘要： 肺癌死亡率在恶性肿瘤中居首。肺癌主要分为小细胞肺癌(SCLC)和非小细胞肺癌(NSCLC)，而NSCLC占75%以上。肺癌发生发展受遗传和表观遗传的协同调控，包括DNA 5-甲基胞嘧啶（5-mC）表观修饰。而5-羟基胞嘧啶(5-hmC)和5-羧甲基胞嘧啶(5-CarC)是由Tet蛋白氧化5-mC产生的两个中间产物，但这两种新的DNA表观修饰如何调控肺癌的发生发展进程并不清楚。我们已经熟练掌握富集5-hmC修饰DNA特异性化学方法和5-CarC修饰DNA抗体免疫共沉淀技术，并收集了50余例非小细胞肺癌组织样品及其癌旁对照，建立了相配套的基因组测序和生物信息分析平台。本项目将利用高通量基因组测序技术，结合生物信息学，研究5-hmC和5-CarC修饰调控NSCLC发生发展进程中DNA甲基化图谱的变异规律，寻找表观遗传调控的关键基因位点、分子标记和药物靶标，为肺癌的诊断和治疗提供理论基础。

中文关键词： 非小细胞肺癌；5hmc；高通量测序；Wnt；

英文摘要： Lung carcinoma is the leading cause of cancer in worldwide.Non-small cell lung cancer(NSCLC) accounts for amlost 75% of such deaths,leaving a minority for small cell lung cancer(SCLC).Lung cancer initiation and progression are driven by a series of genetic and epigenetic alterations that cause either activation of oncogenes, or inactivation of tumor suppressor genes. 5-hydroxymethylcytosine (5-hmC) and 5-carboxymethylcytosine (5-CarC) are generated from 5-mC by the action of the TET (Ten-Eleven-Translocation) enzymes.It had been reported that 5-mC in genomic DNA has important epigenetic fuction in carcinogenesis and progression of lung cancer,little is known about the distribution and function of 5-hmC and 5-CarC. Here,5-hmC and 5-CarC-containing DNA were affinity-enriched by 5hmC specific chemical labeling and 5-CarC immuneprecipitation to and achieved next generation sequencing.Furthermore,with the bioinformation analysis and RNA-seq to generate a comprehensive 5-hmC and 5-carC epigenetic regulations map involved in lung cancer and search for the abnormal epigenetic targets, providing the new insight for the diagnosis and therapy to NSCLC.

英文关键词： NSCLC；5HMC；high-throughtput；wnt；