OBJECTIVETo elucidate the mutation profiles of c-kit/PDGFRα and its associations with clinicopathological characteristics in large scale Chinese gastrointestinal stromal tumors(GISTs).

METHODSClinicopathological data and tumor samples of 1002 GIST patients treated in the Peking University Cancer Hospital from September 2002 to January 2014 were retrospectively collected. Mutation status of c-kit(exons 9, 11, 13, and 17) and PDGFRα(exons 12 and 18) genes were detected by direct sequencing. Association between mutation profiles and clinicopathological features of mutant patients were statistically analyzed.

RESULTSAmong all the 827 mutant patients, c-kit and PDGFRα mutations were found in 798 cases(96.5%, exons 11, 9, 13, and 17 mutations in 669, 99, 18, 12) and 29 cases (3.5%, exons 12 and 18 in 2 and 27), respectively. As for c-kit gene, deletion mutation was most frequent in exon 11(n=325), and then point mutation(n=172), mixed mutation(n=135), and duplication mutation(n=37). The duplication of codons 502-503 was the unique genotype for exon 9 of c-kit gene, and point mutation was the single mutation type for exons 13 and 17 of c-kit gene. Point mutation was the most common mutation for PDGFRα gene with few deletion or mixed mutations. Most deletion mutations of c-kit gene were located in 5' region of exon 11, duplication mutations were mainly located in 3' region of exon 11, and point mutations were focused on codons 556-560. Mutation type of exon 11 was associated with age, gender, primary location, tumor size, karyokinesis image and CD 34 expression(all P<0.05).

CONCLUSIONGISTs are featured by frequent gene mutations, many mutation types, and specificity for mutations in same exons or different exons.