title: Mutations in c-kit gene exons 9 and 13 in gastrointestinal stromal tumors among Japanese.
abstract: Gain-of-function mutation in c-kit proto-oncogene exon 11 has been described in about 20 -- 50% of gastrointestinal stroma tumor (GIST). Recently, additional mutational hot-spots in exon 9 and exon 13 of the c-kit gene have been reported in GISTs without mutations of exon 11, but a subsequent report in a Western population indicated that only a small portion of GISTs (eight of 200 GISTs, 4%) showed mutations in these regions. In this study, we evaluated mutations in exon 9 and exon 13 of the c-kit gene by both polymerase chain reaction-single strand conformation polymorphism analysis and direct sequencing in 48 GISTs in a Japanese population, for which the clinicopathological and immunohistochemical features and mutations in exon 11 had previously been reported. C-kit gene mutation in exon 9, representing insertion of GCC TAT, was identified in only 4 of 48 GISTs (8%), and none of the GISTs had mutations in exon 13. All four GISTs with mutation in exon 9 were high-risk, and the patients died of multiple tumor metastasis. Mutations in exon 9 and exon 13 of the c-kit gene were also rare events in Japanese GISTs and were related to a poor prognosis. These results in Japanese are consistent with those in Western populations, although a preferential occurrence of GISTs with exon 9 mutation in the small intestine, which was suggested in a previous report, was not observed.
authors.affiliation: Department of Pathology, Jichi Medical School, Minamikawachi-machi, Kawachi-gun, Tochigi 329-0498, Japan. ssakurai@jichi.ac.jp
authors.forename: S
authors.initials: S
authors.lastname: Sakurai
authors.forename: S
authors.initials: S
authors.lastname: Oguni
authors.forename: M
authors.initials: M
authors.lastname: Hironaka
authors.forename: M
authors.initials: M
authors.lastname: Fukayama
authors.forename: S
authors.initials: S
authors.lastname: Morinaga
authors.forename: K
authors.initials: K
authors.lastname: Saito
mesh_terms: D000199:Actins / Q000032:analysis; D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000032:analysis; D004273:DNA, Neoplasm / Q000032:analysis; D004379:Duodenal Neoplasms / Q000737:chemistry / Q000235:genetics; D005091:Exons; D006801:Humans; D007150:Immunohistochemistry; D007414:Intestinal Neoplasms / Q000737:chemistry / Q000235:genetics*; D007564:Japan; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D000090063:Proto-Oncogene Mas; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis / Q000235:genetics*; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000737:chemistry / Q000235:genetics*
chemical_list: D000199:Actins; D018952:Antigens, CD34; D004273:DNA, Neoplasm; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D019009:Proto-Oncogene Proteins c-kit