title: Frequent c-Kit gene mutations not only in gastrointestinal stromal tumors but also in interstitial cells of Cajal in surrounding normal mucosa.
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.
authors.affiliation: Division of Oncological Pathology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi 464-8681, Japan.
authors.forename: Naotaka
authors.initials: N
authors.lastname: Ogasawara
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Tsukamoto
authors.forename: Kenichi
authors.initials: K
authors.lastname: Inada
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Mizoshita
authors.forename: Naoko
authors.initials: N
authors.lastname: Ban
authors.forename: Kenji
authors.initials: K
authors.lastname: Yamao
authors.forename: Takashi
authors.initials: T
authors.lastname: Joh
authors.forename: Makoto
authors.initials: M
authors.lastname: Itoh
authors.forename: Masae
authors.initials: M
authors.lastname: Tatematsu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics*; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics* / Q000378:metabolism
chemical_list: D019009:Proto-Oncogene Proteins c-kit