[DNA methylation and cancer--DNA methylation as a target of cancer chemotherapy].
Aberrant epigenetic information, represented by aberrant DNA methylation, plays a large role in carcinogenesis. Hypermethylation of CpG islands in promoter regions can lead to silencing of tumor-suppressor genes, and hypomethylation of the genome could lead to its instability. Epigenetic information is inherited from a cell to its daughter cells without any decay in somatic cells, but shows dynamic changes during embryonic development. Based on the possibility that epigenetic information can be theoretically reversed, attempts are being made to use the aberrant epigenetic information as therapeutic targets. A demethylating agent, 5-aza-2'-deoxycytidine, has been reported to be effective for some hematological malignancies, and its derivatives are being developed. Finally, reports are coming out on methods that can induce sequence-specific methylation changes. Rapid progress in this field is expected.
Miyamoto
Kazuaki
K
Carcinogenesis Division, National Cancer Center Research Institute, 1-1 Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan.
Ushijima
Toshikazu
T
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018899:CpG Islands; D019175:DNA Methylation; D000077209:Decitabine; D044127:Epigenesis, Genetic / Q000502:physiology*; D020868:Gene Silencing; D016147:Genes, Tumor Suppressor; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D017354:Point Mutation; D012097:Repressor Proteins / Q000235:genetics
D000964:Antimetabolites, Antineoplastic; C411744:DMAP1 protein, human; C485852:Dmap1 protein, mouse; D012097:Repressor Proteins; D000077209:Decitabine; D001374:Azacitidine