Fig. 1

DNA methylation and deregulation of the genome in carcinogenesis. Methylation of cytosine within CpG dinucleotides is catalyzed by DNMTs. S-adenosylmethionine (SAM) donates methyl groups and is converted to S-adenosylhomocysteine (SAH). In normal cells (lower left), CpG islands are often associated with gene promoters and are resistant to DNA methylation. Gene expression can occur and is highly correlated with high levels of gene body (genic) methylation. CpG-poor regions (intergenic), except for enhancers, are typically methylated, while CpG-poor promoters are silenced by DNA methylation unless gene expression is required in specific tissue. In cancer cells (lower right), CpG islands are prone to DNA hypermethylation, which results in aberrant gene silencing (e.g., of tumor suppressor genes). Concomitant hypomethylation of intergenic regions and CpG-poor promoters contributes to genomic instability and aberrant gene expression (e.g., of oncogenes), respectively. Green circle, unmethylated CpG; purple circle, methylated CpG