title: Unmasking risk loci: DNA methylation illuminates the biology of cancer predisposition: analyzing DNA methylation of transcriptional enhancers reveals missed regulatory links between cancer risk loci and genes.
abstract: Paradoxically, DNA sequence polymorphisms in cancer risk loci rarely correlate with the expression of cancer genes. Therefore, the molecular mechanism underlying an individual's susceptibility to cancer has remained largely unknown. However, recent evaluations of the correlations between DNA methylation and gene expression levels across healthy and cancerous genomes have revealed enrichment of disease-related DNA methylation variations within disease-associated risk loci. Moreover, it appears that transcriptional enhancers embedded in cancer risk loci often contain DNA methylation sites that closely define the expression of prominent cancer genes, despite the lack of significant correlations between gene expression levels and the surrounding disease-associated polymorphic sequences. We suggest that DNA methylation variations may obscure the effect of co-residing risk sequence alleles. Analysis of enhancer methylation data may help to reveal the regulatory circuits underlying predisposition to cancers and other common diseases.
authors.affiliation: Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, Hebrew University-Hadassah Medical School, Jerusalem, Israel; School of Computer Science and Engineering, Hebrew University, Jerusalem, Israel.
authors.forename: Dvir
authors.initials: D
authors.lastname: Aran
authors.forename: Asaf
authors.initials: A
authors.lastname: Hellman
mesh_terms: D000818:Animals; D019175:DNA Methylation / Q000235:genetics*; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D009369:Neoplasms / Q000235:genetics*; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics
keywords: DNA methylation; cancer; common human disease; disease risk loci; epigenomics; gene regulation; transcriptional enhancers