TITLE:
Epigenetic Aberrant Hypermethylation of DNA in Endometrial Cancer: Application as a Biomarker
AUTHORS:
Asuka Ono, Iori Kisu, Kouji Banno, Megumi Yanokura, Kenta Masuda, Yusuke Kobayashi, Kosuke Tsuji, Arisa Ueki, Wataru Yamagami, Hiroyuki Nomura, Nobuyuki Susumu, Daisuke Aoki
KEYWORDS:
Epigenetics, Endometrial Cancer, Aberrant DNA Hypermethylation, hMLH1, CHFR, Biomarker
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.2 No.5,
December
31,
2011
ABSTRACT: Endometrial cancer is the seventh most common cancer worldwide among females and accounts for about 40% of cancers of the uterus in Japan. An increase in incidence and a reduction in onset age of this disease are also likely, which makes it important to define the pathogenesis and develop effective treatment. However, the mechanism of canceration in the endometrium is unclear and development of endometrial cancer cannot be explained only by mutations of cancer-related genes. In contrast, epigenetic analyses have shown the importance of aberrant DNA hypermethylation in the canceration mechanism. In development of type 1 endometrial cancer, breakdown of the DNA mismatch repair system plays a large role, with changes in the human mutL homologue 1 (hMLH1) gene being of most importance. Studies to detect aberrant DNA hypermethylation of cancer cells present in microscopic amounts in vivo and to apply these data to diagnosis of cancer have been started. Epigenetic changes have also been examined as a marker of sensitivity to anticancer drugs. Aberrant hypermethylation of checkpoint with forkhead-associated and ring finger (CHFR), a mitotic phase checkpoint gene, is correlated with sensitivity to treatment with microtubule inhibitors and may be a marker for the response of endometrial cancer to anticancer drugs. Epigenetic aberrant DNA methylation of other genes may also be useful as clinical biomarkers for diagnosis and treatment of endometrial cancer.