Carcinogenic mechanisms of endometrial cancer: Involvement of genetics and epigenetics

Kouji Banno, Megumi Yanokura, Miho Iida, Kenta Masuda, Daisuke Aoki

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

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 hMLH1; mutation of PTEN, β-catenin and K-ras genes in type I endometrial cancer and of HER-2/neu and p53 genes in type II endometrial cancer; hypermethylation of SPRY2, RASSF1A, RSK4, CHFR and CDH1; and methylation of tumor suppressor microRNAs, including miR-124, miR-126, miR-137, miR-491, miR-129-2 and miR-152. 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.

Original languageEnglish
Pages (from-to)1957-1967
Number of pages11
JournalJournal of Obstetrics and Gynaecology Research
Volume40
Issue number8
DOIs
Publication statusPublished - 2014

Fingerprint

Endometrial Neoplasms
DNA Mismatch Repair
Epigenomics
Methylation
erbB-2 Genes
Mutation
Estrogens
Carcinogenesis
Genes
Catenins
ras Genes
p53 Genes
Tumor Suppressor Genes
MicroRNAs
Oncogenes
Germ Cells
Neoplasms

Keywords

  • DNA hypermethylation
  • DNA mismatch repair
  • endometrial cancer
  • epigenetics
  • genetics

ASJC Scopus subject areas

  • Obstetrics and Gynaecology

Cite this

Carcinogenic mechanisms of endometrial cancer : Involvement of genetics and epigenetics. / Banno, Kouji; Yanokura, Megumi; Iida, Miho; Masuda, Kenta; Aoki, Daisuke.

In: Journal of Obstetrics and Gynaecology Research, Vol. 40, No. 8, 2014, p. 1957-1967.

Research output: Contribution to journalArticle

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