distinct functional patterns of gene promoter hypomethylation and hypermethylation in cancer genomes不同功能的基因启动子hypomethylation和癌症基因组甲基化模式.pdfVIP

Distinct Functional Patterns of Gene Promoter Hypomethylation and Hypermethylation in Cancer Genomes 1 1 1 1 1 1 1 1 Xiaopei Shen , Zheng He , Hongdong Li , Chen Yao , Yang Zhang , Lang He , Shan Li , Jian Huang , Zheng Guo1,2* 1 Bioinformatics Centre, School of Life Science, University of Electronic Science and Technology of China, Chengdu, China, 2 College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China Abstract Background: Aberrant DNA methylation plays important roles in carcinogenesis. However, the functional significance of genome-wide hypermethylation and hypomethylation of gene promoters in carcinogenesis currently remain unclear. Principal Findings: Based on genome-wide methylation data for five cancer types, we showed that genes with promoter hypermethylation were highly consistent in function across different cancer types, and so were genes with promoter hypomethylation. Functions related to ‘‘developmental processes’’ and ‘‘regulation of biology processes’’ were significantly enriched with hypermethylated genes but were depleted of hypomethylated genes. In contrast, functions related to ‘‘cell killing’’ and ‘‘response to stimulus’’, including immune and inflammatory response, were associated with an enrichment of hypomethylated genes and depletion of hypermethylated genes. We also observed that some families of cytokines secreted by immune cells, such as IL10 family cytokines and chemokines, tended to be hypomethylated in various cancer types. These results provide new hints for understanding the distinct functional roles of genome-wide hypermethylation and hypomethylation of gene promoters in carcinogenesis. Conclusions: