Mutations of RAS genes in endometrial polyps

Takashi Takeda, Kouji Banno, Yusuke Kobayashi, Masataka Adachi, Megumi Yanokura, Eiichiro Tominaga, Kenjiro Kosaki, Daisuke Aoki

Research output: Contribution to journalArticle

Abstract

Endometrial polyps are common, yet the molecular mechanisms underlying their formation and progression remain unclear. We examined gene mutations possibly related to the pathogenesis of endometrial polyps, as well as to their clinical features. Four premenopausal patients with endometrial polyps, who were not under drug treatment, were recruited. Whole exomes of endometrial polyps and peripheral blood lymphocytes were analyzed by next-generation sequencing, and somatic mutations were derived by subtraction. Then, 35 samples of endometrial polyps and 12 samples of atypical polypoid adenomyoma were newly recruited to validate the identified mutations by polymerase chain reaction-reverse sequence specific oligonucleotide method. The mutations were also analyzed in separate stromal and glandular components of the polyps after laser-capture microdissection. Whole exome sequencing revealed that KRASmutations were the only type of mutation detectable in multiple cases (2/4). Targeted mutation analysis revealed that 16 of 35 samples (45.7%) of endometrial polyps harbored RAS mutations. Mutation-positive cases exhibited a significantly higher number of endometrial polyps (3.25±2.70 vs. 1.74±0.87, P=0.045). Laser-capture microdissection in NRAS-mutated endometrial polyps revealed that both stromal and glandular components harbored RAS mutations. There was no RAS mutation in 12 samples of atypical polypoid adenomyoma. This is the first report demonstrating that pathogenic RAS mutations are frequent in non-treated endometrial polyps. RAS mutations may have an important role in tumorigenesis and in the formation of multiple endometrial polyps.

Original languageEnglish
Pages (from-to)2303-2308
Number of pages6
JournalOncology reports
Volume42
Issue number6
DOIs
Publication statusPublished - 2019 Jan 1

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Keywords

  • Atypical polypoid adenomyoma
  • Benign tumors
  • Endometrial cancer
  • Endometrial polyp
  • RAS mutation
  • Tumorigenesis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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