肺癌组织内不同肿瘤细胞群体的遗传变异与演化规律

项目名称： 肺癌组织内不同肿瘤细胞群体的遗传变异与演化规律

项目编号： No.91231113

项目类型： 重大研究计划

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： 杨祖玉

作者单位： 中国科学院北京基因组研究所

项目金额： 100万元

中文摘要： 癌症是21 世纪人类面临的最大挑战之一。了解癌症的发生发展规律是预防、控制和治疗癌症的关键。随着基因组学的推进，从微观层次上了解肿瘤细胞群体的发生发展规律成为了可能。癌症发生具有很强的个体特异性，近年来肿瘤基因组研究显示，寻找共有突变的研究策略受到极大挑战。探索肿瘤发生机制需要新的研究策略。由于肿瘤组织内部微环境的异质性，使得肿瘤组织不同部位的选择压力不尽相同，并驱导不同区域的肿瘤细胞群的适应性演化。本项目旨在通过对多例肺癌肿瘤组织进行微取样，即对同一个肿瘤组织30~50个不同部位的肿瘤细胞群体进行取样、深度测序，并结合遗传漂变理论和选择的进化动力学分析来界定不同遗传组成的细胞克隆群体，考察它们之间适应度的差异并鉴定导致适应度改变的关键基因。进一步对体细胞突变特点和进化过程有全面的了解，揭示肿瘤细胞的发生和增殖进程的动态过程。

中文关键词： 遗传多样性；肝细胞肝癌；进化驱动力；早期转移；适应性进化

英文摘要： Cancer is the most challenging disease in the 21st century. It is the key step to prevention, control and cure cancer with the development of understanding of cancer. With the advance of genomics, it is a good chance to study the microevolution of tumor cell population during the development of the tumor cells. Cancer is a kind of personalized disease, and cancer genomics studies in recent years have shown that the strategy of looking for common mutation is facing a great challenge. Exploring tumor mechanisms need new research strategies. Because of the heterogeneity of tumor microenvironment, tumor cell populations in different locations of a tumor tissue face different selection pressures, and it make different regions of the tumor cell populations adaptive to local microenvironment. We plan to do micro-sampling of lung cancer tumor tissues, around 30~50 tumor cell populations, then deep sequencing. Combined with genetic drift theory and the evolutionary dynamics analysis on cellular selection, we could define different tumor cell populations with different genetic composition and examine the fitness differences between those tumor cell populations and identify the important mutations driving tumor cell growth in each tumor case. By tracing the tumor cell lineages, we would have a comprehensive understanding o

英文关键词： Genetic diversity；hepatocellular carcinoma (HCC)；evolutionary forces；early migration；adaptive evolution