肿瘤转移是基因突变筛选及克隆竞争的微进化过程，也是基因突变和表观遗传变异协同作用适应新的微环境过程。近来发现，肿瘤是个体差异非常大的疾病，每例患者肿瘤发生和转移都有其独特的驱动变异,以往寻找共有突变的研究策略不适合肿瘤个性化特点。而且，目前对基因变异和表观遗传变异如何协同驱动肿瘤细胞转移到其它器官中，且肿瘤细胞如何适应不同的微环境等核心科学问题还有很多未知领域。因此，本课题以进化遗传学的理论为指导，结合基因组学、细胞生物学和分子遗传手段，着重探索肿瘤转移的分子机理。通过对原发灶、非癌对照组织、转移灶和转移灶周围对照组织进行基因组和表观遗传组的比较分析，在每一例肿瘤患者中寻找肿瘤转移过程中关键的基因突变和表观遗传变异，分析遗传突变和表观遗传变异的协同作用，揭示肿瘤适应微环境发生转移的分子机理，为肿瘤个体化治疗提供理论指导。

Tumor metastasis is a micro-evolutionary process which has been selected by the clone competition. The coordination of genetic and epigenetic alterations drives tumor cells to evolve the fitness to the distinct new micro-environment. Recent studies show there are great variances among individual cancer patients. Cancer is a personalized disease. Previous association studies have showed that common variants implicated account for only a small proportion of the genetic component and much of the missing heritability lies within the huge class of relatively or very rare genetic variants which were not represented in the association studies. However, each cancer patient has his own driver mutations. But it is still limited understood how genetic mutations coordinate with epigenetic changes drive the tumor cells to metastasize to other organs and evolve the fitness new microenvironments. Here, we will combine genomics, cell biology and genetic methods to study the mechanism of metastasis by population evolutionary strategy. We will compare the genomic and epigenomic features among primary tumor, matched non-tumor control tissue, metastasis tumor, and non-tumor control tissue of metastasized organ. We aim to find both the genetic and epigenetic driver mutations during tumor metastasis. We will illustrate the mechanism how genetics and epigenetics coordinate during tumor metastasis, and how metastasis tumor cells fit the new environments. Our studies will guide the personalized medicine for cancer patients