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 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 clinicopatho‐logical 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.