Mutation profiles of c-kit/PDGFRα and its associations with clinicopathological characteristics in Chinese gastrointestinal stromal tumors: analysis of 827 cases / 中华胃肠外科杂志

ABSTRACT

<p><b>OBJECTIVE</b>To elucidate the mutation profiles of c-kit/PDGFRα and its associations with clinicopathological characteristics in large scale Chinese gastrointestinal stromal tumors(GISTs).</p><p><b>METHODS</b>Clinicopathological 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.</p><p><b>RESULTS</b>Among 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).</p><p><b>CONCLUSION</b>GISTs are featured by frequent gene mutations, many mutation types, and specificity for mutations in same exons or different exons.</p>