DNA methylation is a covalent modification occuring in mammals mainly in CpG sequences on the fifth position of a cytosine ring. The reaction is catalyzed by specific enzymes, DNA methyltransferases, that transfer a methyl group from S-adenosyl-L-methionine (SAM), the ubiquitous methyl donor, onto the cytosine residue. When CpG sequences in promoters and other regulatory regions are methylated, it blocks access of the transcriptional machinery and the gene is consequently inactive. 

 

Every healthy tissue has a precise DNA methylation pattern that changes during cancer development forming a cancer-specific design. Hypermethylation of tumor suppressor genes linked to transcriptional silencing, global DNA demethylation associated with genome rearrangements and instability, and promoter hypomethylation linked to activation of oncogenes and prometastatic genes are hallmarks of nearly all types of cancer.