中文摘要：

DNA甲基化是一种重要的表观遗传学修饰,在基因的转录调控方面具有重要的作用. 异常的DNA甲基化可以导致癌症等复杂疾病发生,癌基因相关的DNA甲基化调控位点的识别对于解析癌症的发生发展机制及识别新的癌症标记具有重要意义. 本研究通过整合The Cancer Genome Atlas（ TCGA）的泛癌症基因组的高通量甲基化谱和基因表达谱,识别癌基因相关的DNA甲基化调控位点. 对于每种癌症分批次计算CpG位点甲基化与相关基因表达之间的相关性,并筛选调控下游基因的CpG位点（包括强调控位点、弱调控位点和不调控位点） ,结果表明仅有一半的CpG位点对下游基因具有调控作用;对癌症间共享的调控位点的分析发现不同癌症间共享的调控位点不尽相同,表明癌症特异的甲基化调控位点的存在. 进一步地,对差异甲基化和差异表达基因的功能富集分析揭示了受甲基化调控的基因确实参与了癌症发生发展相关的功能. 本研究的结果是对当前甲基化调控位点集的重要补充,也是识别癌症新型分子标记特征的重要资源.

英文摘要：

DNA methylation is an important epigenetic modification,which plays an important role in the regulation of gene transcription.Abnormal DNA methylation may lead to cancer and disease,and identifying oncogene-related DNA methylation gene regulatory sites is important for the development of mechanisms to resolve the occurrence of cancer and identify new cancer markers. In this study,we integrate high-throughput DNA methylation profiling and gene expression profiling of pan-cancer genome in TCGA, then identify oncogene-related DNA methylation regulation sites.For each cancer,we calculate the correlation between methylation of CpG sites and gene expression, and filter the CpG sites, which regulate downstream genes（ including strong regulatory sites, weak regulatory sites and not regulatory sites）.The results show thatonly half of the CpG sites regulate the downstream genes.Analyzing of regulatory sites that is shared between cancers show that regulatory sites are not necessarily the same in different cancer,and the presence of cancer-specific methylation regulatory sites. Moreover,gene function enrichment analysis of differential DNA methylation and differentially expressed genes show that genes regulated by methylation are indeed involved in the development of cancer-related functions. The results of this study are an important supplementation to the current DNA methylation regulatory sites set, and an important resource to identify new molecular markers characteristics of cancer.