Frequent c-Kit gene mutations not only in gastrointestinal stromal tumors but also in interstitial cells of Cajal in surrounding normal mucosa

Naotaka Ogasawara, Tetsuya Tsukamoto, Kenichi Inada, Tsutomu Mizoshita, Naoko Ban, Kenji Yamao, Takashi Joh, Makoto Itoh, Masae Tatematsu

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Gastrointestinal stromal tumors (GISTs) are thought to originate from mesenchymal stem cells that differentiate toward the interstitial cells of Cajal (ICCs). The frequent occurrence of activating mutations involving exon 11 of c-Kit gene in sporadic GISTs indicates an important role in genesis of this tumor type. In the present study we examined c-Kit gene mutations in a series of GISTs and also in ICCs of surrounding normal tissues. Samples from 18 patients were monitored immunohistochemically for c-Kit expression and microdissected for sequencing analysis of exons 9, 11, 13, and 17 of the c-Kit gene. It was revealed to be mutated in exon 11 or adjacent introns in 9 out of the total of 18 (50.0%) GISTs. In 6 (33.3%) cases, mutations in ICCs were also detected in the same exon. With stomach GISTs, 8 of 16 (50.0%) cases harbored mutations and 4 had mutations in background ICCs (25.0%). In contrast counterpart ICCs in gastric cancer cases harbored no c-Kit gene mutations (0 out of 24=0%) (P<0.02). ICCs undergoing c-Kit mutation as a possible early initiation step in GIST tumorigenesis may thus have pre-neoplastic potential.

Original languageEnglish
Pages (from-to)199-210
Number of pages12
JournalCancer Letters
Volume230
Issue number2
DOIs
Publication statusPublished - 18-12-2005
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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