title: Distinct functional patterns of gene promoter hypomethylation and hypermethylation in cancer genomes.
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.
  
  
  RESULTS
  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
  Genes with promoter hypermethylation and hypomethylation are highly consistent in function across different cancer types, respectively, but these two groups of genes tend to be enriched in different functions associated with cancer. Especially, we speculate that hypomethylation of gene promoters may play roles in inducing immunity and inflammation disorders in precancerous conditions, which may provide hints for improving epigenetic therapy and immunotherapy of cancer.
authors.affiliation: Bioinformatics Centre, School of Life Science, University of Electronic Science and Technology of China, Chengdu, China.
authors.forename: Xiaopei
authors.initials: X
authors.lastname: Shen
authors.forename: Zheng
authors.initials: Z
authors.lastname: He
authors.forename: Hongdong
authors.initials: H
authors.lastname: Li
authors.forename: Chen
authors.initials: C
authors.lastname: Yao
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Lang
authors.initials: L
authors.lastname: He
authors.forename: Shan
authors.initials: S
authors.lastname: Li
authors.forename: Jian
authors.initials: J
authors.lastname: Huang
authors.forename: Zheng
authors.initials: Z
authors.lastname: Guo
mesh_terms: D019175:DNA Methylation; D016678:Genome; D006801:Humans; D009369:Neoplasms / Q000235:genetics*; D011401:Promoter Regions, Genetic