Review Article Diagnostic and Therapeutic Applications of Epigenetics

Epigenetic abnormalities, such as aberrant methylation of CpG islands, are inherited over cell divisions, and play important roles in carcinogenesis. Aberrant methylation of CpG islands specific to tumor cells can be used as a marker to detect cancer cells or cancer-derived DNA, taking advantage of the high sensitivity of methods to detect aberrant methylation. Methylations of specific genes or methylation patterns of groups of genes were found to be associated with responses to chemotherapeutics and prognosis. Methylation in non-cancerous tissues is now attracting attention as a tumor risk marker, and is emerging as a target for cancer prevention. Epigenetic alterations are potentially reversible. The use of DNA demethylating agents has turned out to be effective for hematological malignancies, and is being tested in solid tumors. Histone deacetylase inhibitors and methods for gene-specific epigenetic modification are being developed. Application of epigenetics to cancer diagnostics and therapeutics, and possibly to cancer prevention, is coming into clinics. Key words: epigenetics – CpG island – DNA methylation – tumor marker – cancer therapy The clinical usefulness of cancer epigenetics is becoming clear. Many kinds of tumor-specific aberrant DNA methylation have been identified (1,2), and these are being tested as tumor mark-ers (3,4). Demethylating agents have proven to be effective as chemotherapeutic drugs (5,6). The heritable nature and the plasticity of epigenetic information, which could sound contra-dictory, underlie these clinical applications. In this review, we would like briefly to describe basic aspects of epigenetics, and then focus on the current status of its clinical applications