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J.Jpn. Surg. Soc.. 113(2): 191-196, 2012
Feature topic
APPLICATION OF EPIGENETICS TO CANCER DIAGNOSIS AND THERAPY
Epigenetic modifications are responsible for the stable maintenance of cellular phenotypes and consist of DNA methylation and histone modifications. Epigenetic abnormalities can be causally involved in cancer development (driver) and can also be present as a passenger. Aberrant DNA methylation has unique characteristics different from point mutations and is utilized as a diagnostic target. First, aberrant DNA methylation can be present at a high level in noncancerous tissues, and because its level can correlate with cancer risk, it is useful as a cancer risk marker. Second, aberrant DNA methylation can be detected with high sensitivity and therefore it is used to detect cancer cells. Third, DNA methylation is stable at different time points, such as at biopsy and during chemotherapy, and provides a good source of biomarkers. In addition, resistance to contaminating cells makes DNA methylation useful in genome-wide screening of biomarkers for various clinicopathologic characteristics. From the therapeutic viewpoint, DNA demethylating agents have been approved for the treatment of myelodysplastic syndrome and histone deacetylase inhibitors for the treatment of cutaneous T-cell lymphoma. The next steps include increasing the specificity for target genes, the development of biomarkers for dose and response studies, and establishing a strategy to select drugs for combination therapy. The further use of epigenetics for diagnosis and therapy is warranted.
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