Mutations in c-kit gene exons 9 and 13 in gastrointestinal stromal tumors among Japanese

Gain-of-function mutation in c-kit proto-oncogene exon 11 has been describe d in about 20-50% of gastrointestinal stroma tumor (GIST), Recently, additi onal 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 GLSTs (eight o f 200 GISTs, 4%) showed mutations in these regions. In this study, we evalu ated mutations in exon 9 and exon 13 of the c-kif gene by both polymerase c hain reaction-single strand conformation polymorphism analysis and direct s equencing in 48 GISTs in a Japanese population, for which the clinicopathol ogical and immunohistochemical features and mutations in exon 11 had previo usly been reported, C-kil gene mutation in exon 9, representing insertion o f 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 exo n 9 and exon IJ of the c-kit gene were also rare events in Japanese GISTs a nd were related to a poor prognosis. These results in Japanese are consiste nt 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.