Carcinogenic mechanisms of endometrial cancer: Involvement of genetics and epigenetics. Issue 8 (August 2014)

• Record Type: Journal Article
• Authors: Banno, Kouji; Yanokura, Megumi; Iida, Miho; Masuda, Kenta; Aoki, Daisuke
• Is Part Of: Journal of obstetrics and gynaecology research. Volume 40:Issue 8(2014:Aug.)
• Page Start: 1957
• Page End: 1967
• Publication Date: 2014-08
• Subjects: Gynecology -- Periodicals; Obstetrics -- Periodicals; 618.1005
• DOI: 10.1111/jog.12442
• Languages: English
• ISSNs: 1341-8076

Abstract

<abstract abstract-type="main"> <title>Abstract</title> <p>Endometrial cancer is increasing worldwide and the number of patients with this disease is likely to continue to grow, including younger patients. Many endometrial cancers show estrogen‐dependent proliferation, but the carcinogenic mechanisms are unknown or not completely explained beyond mutations of single oncogenes and tumor suppressor genes. Possible carcinogenic mechanisms include imbalance between endometrial proliferation by unopposed estrogen and the mismatch repair (MMR) system; hypermethylation of the MMR gene <italic>hMLH1</italic>; mutation of <italic>PTEN</italic>, <italic>β‐catenin</italic> and <italic>K‐ras</italic> genes in type I endometrial cancer and of <italic>HER‐2/neu</italic> and <italic>p53</italic> genes in type II endometrial cancer; hypermethylation of <italic>SPRY2</italic>, <italic>RASSF1A</italic>, <italic>RSK4</italic>, <italic>CHFR</italic> and <italic>CDH1</italic>; and methylation of tumor suppressor microRNAs, including <italic>miR‐124</italic>, <italic>miR‐126</italic>, <italic>miR‐137</italic>, <italic>miR‐491</italic>, <italic>miR‐129‐2</italic> and <italic>miR‐152</italic>. Thus, it is likely that the carcinogenic mechanisms of endometrial cancer involve both genetic and epigenetic changes. Mutations and methylation of MMR genes induce various oncogenic changes that cause carcinogenesis, and both MMR mutation in germ cells and methylation patterns may be inherited over generations and cause familial tumorigenesis. Determination of the detailed carcinogenic mechanisms will be useful for prevention and diagnosis of endometrial cancer, risk assessment, and development of new treatment strategies targeting MMR genes.</p> </abstract>