Figure 1.

Models for the role of 5-methylcytosine in cancer. [1] Signature mutations in the form of C → T transitions at methylated CpG sites are the hallmark of hydrolytic deamination of 5-methylcytosine and commonly produce mutations in tumor suppressor genes such as p53. [2] Abnormal silencing of tumor suppressor genes can occur through the epigenetic effects of DNA methylation at CpG islands, which may be localized to the promoters of growth regulatory genes such as p16, Rb, and VHL. [3] Induction of chromosomal instability may result from the inability of a cell to carry out de novo methylation as proposed in the report by Lengauer et al. (15). Circles represent cytosines located at CpG dinucleotides; solid circles indicate methylated cytosines, open circles indicate unmethylated cytosines. T.S., tumor suppressor gene; PRO, promoter; LTR, long terminal repeat.