Epigenetic DNA hypermethylation: clinical applications in endometrial cancer (Review).
Improvements in epigenetics have resulted in identification of a number of genes with aberrant hypermethylation associated with systematic occurrence of cancer. It is now evident that aberrant hypermethylation inactivates cancer-related genes including those associated with cell cycle control, apoptosis, and DNA repair. An epigenetic analysis of DNA hypermethylation in type I endometrial cancer has led to a proposed mechanism for endometrial carcinogenesis. Reduced DNA mismatch repair due to loss of hMLH1 expression is thought to have a major role in carcinogenesis and these findings open up approaches to prevention, diagnosis, risk assessment, and treatment of type I endometrial cancer. Aberrant DNA hypermethylation can be detected with high sensitivity for identification of cancer cells in sputum, blood and other biopsy materials, including in endometrial cancer specimens. There have been many attempts to use methylation inhibitors as anticancer agents, and epigenetic abnormalities may be useful as biomarkers of anticancer drug sensitivity and to identify biological characteristics of tumor cells for determination of treatment options based on hypermethylation. For example, aberrant hypermethylation of the CHFR gene is correlated with cellular sensitivity to microtubule inhibitors, and this may be useful in treatment of type I endometrial cancer. An ultimate objective of epigenetics is to identify the type of hereditary methylation responsible for cancer, with the goal of improved diagnosis and treatment based on control of methylation.
Muraki
Yuriko
Y
Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo 160-8582, Japan.
Banno
Kouji
K
Yanokura
Megumi
M
Kobayashi
Yusuke
Y
Kawaguchi
Makiko
M
Nomura
Hiroyuki
H
Hirasawa
Akira
A
Susumu
Nobuyuki
N
Aoki
Daisuke
D
D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics*; D016889:Endometrial Neoplasms / Q000235:genetics*; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics
D004273:DNA, Neoplasm; D009363:Neoplasm Proteins