THE ROLE OF DNA METHYLATION IN CANCER GENETICS AND EPIGENETICS

The past few years have seen a wider acceptance of a role for DNA meth ylation in cancer. This can be attributed to three developments. First , the documentation of the over-representation of mutations at CpG din ucleotides has convincingly implicated DNA methylation in the generati on of oncogenic point mutations. The second important advance has been the demonstration of epigenetic silencing of tumor suppressor genes b y DNA methylation. The third development has been the utilization of e xperimental methods to manipulate DNA methylation levels. These studie s demonstrate that DNA methylation changes in cancer cells are not mer e by-products of malignant transformation, but can play an instrumenta l role in the cancer process. It seems clear that DNA methylation play s a variety of roles in different cancer types and probably at differe nt stages of oncogenesis. DNA methylation is intricately involved in a wide diversity of cellular processes. Likewise, it appears to exert i ts influence on the cancer process through a diverse array of mechanis ms. It is our task not only to identify these mechanisms, but to deter mine their relative importance for each stage and type of cancer. Our hope then will be to translate that knowledge into clinical applicatio ns.