title: C-kit gene abnormalities in gastrointestinal stromal tumors (tumors of interstitial cells of Cajal.
abstract: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the GI tract, and expresses KIT and CD34 in most cases. Gain-of-function mutation of the c-kit proto-oncogene has been described, but its significance in GIST has not yet been fully evaluated. Mutation in exon 11 of the c-kit gene was determined by both polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis and direct sequencing in primary and metastatic GISTs and esophageal leiomyomas in Japanese subjects. C-kit gene mutation was identified in 15 of 48 primary GISTs (31%), four of seven metastatic GISTs, but none of the leiomyomas. Three mutations were mis-sense point mutations, and 16 were in-frame deletions of 3-48 bp. C-kit gene mutation was observed equally in low- and high-risk groups, and was not related to any clinical and pathologic factors, phenotypes or Ki-67 labeling index (LI) of tumor cells. In five of 15 deletion mutations (four in primary tumors and one in a metastatic tumor), the mutations were present at the distal location of exon 11 of the c-kit gene, which was a minor mutation in previous reports from Finland and the USA. C-kit gene mutations in GIST are not always related to a poor prognosis, but further comparative studies are necessary in Western and Japanese populations.
authors.affiliation: Department of Pathology, Jichi Medical School, Kawachi-gun, Tochigi. ssakurai@jichi.ac.jp
authors.forename: S
authors.initials: S
authors.lastname: Sakurai
authors.forename: T
authors.initials: T
authors.lastname: Fukasawa
authors.forename: J M
authors.initials: JM
authors.lastname: Chong
authors.forename: A
authors.initials: A
authors.lastname: Tanaka
authors.forename: M
authors.initials: M
authors.lastname: Fukayama
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D001483:Base Sequence; D005260:Female; D006801:Humans; D007414:Intestinal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D017354:Point Mutation; D000090063:Proto-Oncogene Mas; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D017384:Sequence Deletion; D013274:Stomach Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D019009:Proto-Oncogene Proteins c-kit