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.
Miyamoto
Kazuaki
K
Carcinogenesis Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045 Japan.
Ushijima
Toshikazu
T
D014408:Biomarkers, Tumor / Q000235:genetics; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D019942:Genes, p16; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000235:genetics; D006258:Head and Neck Neoplasms / Q000175:diagnosis / Q000235:genetics; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics; D008297:Male; D009369:Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000517:prevention & control; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000235:genetics; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000235:genetics
D014408:Biomarkers, Tumor; D007527:Isoenzymes; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D006655:Histone Deacetylases