C-kit gene abnormalities in gastrointestinal stromal tumors (tumors of interstitial cells of Cajal)

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 significa nce 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 con formation 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 IS of 48 primary GISTs (31%), four of seve n metastatic GISTs, but none of the leiomyomas. Three mutations were mis-se nse 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 rel ated to any clinical and pathologic factors, phenotypes or Ki-67 labeling i ndex (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 d istal 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 ar e necessary in Western and Japanese populations.