DNA methylation and cancer

The methylation of DNA is an epigenetic modification that can play an impor tant role in the control of gene expression in mammalian cells. The enzyme involved in this process is DNA methyltransferase, which catalyzes the tran sfer of a methyl group from S-adenosyl-methionine to cytosine residues to f orm 5-methylcytosine, a modified base that is found mostly at CpG sites in the genome. The presence of methylated CpG islands in the promoter region o f genes can suppress their expression. This process may be due to the prese nce of 5-methylcytosine that apparently interferes with the binding of tran scription factors or other DNA-binding proteins to block transcription. In different types of tumors, aberrant or accidental methylation of CpG island s in the promoter region has been observed for many cancer-related genes re sulting in the silencing of their expression. How this aberrant hypermethyl ation takes place is not known. The genes involved include tumor suppressor genes, genes that suppress metastasis and angiogenesis, and genes that rep air DNA suggesting that epigenetics plays an important role in tumorigenesi s. The potent and specific inhibitor of DNA methylation, 5-aza-2'-deoxycyti dine (5-AZA-CdR) has been demonstrated to reactivate the expression most of these "malignancy" suppressor genes in human tumor cell lines. These genes may be interesting targets for chemotherapy with inhibitors of DNA methyla tion in patients with cancer and this may help clarify the importance of th is epigenetic mechanism in tumorigenesis. (C) 2000 Wiley-Liss, Inc.