DNA methylation is a major determinant in the epigenetic silencing of genes. It is a complex process wherein three DNA methyltransferases catalyze the addition of a methyl group from S-adenosyl-L-methionine to the 5-carbon position of cytosine. It is involved in regulating transcription and chromatin structure, and protects cells from invading foreign DNA. DNA methylation occurs predominantly within the CpG dinucleotide and is one of the most prevalent epigenetic modifications of DNA in mammalian genomes. CpG sites are important spots for mutations in the germline and for inactivating mutations in tumor suppressor genes. About 25% of all mutations in the p53 gene in human cancers occurs at CpG sites. The bulk of the genome in cancer cells becomes hypomethylated, in particular the normally hypermethylated and silent regions containing the repetitive elements are substantially demethylated. In a number of experimental models of carcinogenesis, this decrease in numbers of methyl groups appears to begin early in tumor progression. References:
Clark, S.J., and Melki, J. 2002. Oncogene 21, 5380; Robertson, K.D. 2002. Oncogene 21, 5361; El-Osta, A., and Wolffe, A.P. 2000. Gene Expr. 9, 63; Christman, J.K., et al. 1993. Carcinogenesis 14, 551; Cooper, D.N., and Youssoufian, H. 1988. Hum. Genet. 78, 151; Feinberg, A.P., et al. 1988. Cancer Res. 48, 1159. |
