Involvement of DNA methylation in human carcinogenesis.

It is now generally accepted that the presence of 5-methylcytosine (5mC) in human DNA has both a genetic and an epigenetic effect on cellular development, differentiation and transformation. First, 5mC is more unstable than its unmethylated counterpart cytosine. Hydrolytic deamination of 5mC leads to a G/T mismatch and subsequently, if unrepaired, to a C-->T transition mutation. Sites of DNA methylation are mutational hotspots in many human tumors. Second, DNA methylation of promoter regions is often correlated with the down regulation of the corresponding gene. Both of these effects have fundamental consequences for basic functions of the cell like cellular differentiation, the development of cancer and possibly other diseases, and on the evolutionary process. Recent hypotheses also propose a role for methylation in the process of aging. In this review we will describe recent findings and hypotheses about the function of 5mC in DNA with the focus on its involvement in human carcinogenesis.