Detection of KIT and PDGFRA mutations in gastrointestinal stromal tumors

Abstract

Objective To investigate the mutations of KIT and PDGFRA genes and their clinical significance in Chinese patients with gastrointestinal stromal tumor (GIST). Methods Molecular analysis of KIT exons 9, 11, 13, 17 and PDGFRA exons 12, 18 was performed on 136 patients from a single institute. Specimens from imatinib-resistant tumors in 8 cases were studied to identify molecular correlations of imatinib resistance. Results KIT mutations was found in 111 patients (81.6% ) , among whom exons 11 and 9 were mutated in 95 (69.8% ) and 16 (11.8% ) patients, respectively. Wild types of KIT and PDGFRA was identified in the other 25 patients (18.4% ). Inflamed deletions in the 5 ' end were most common molecular changes in mutated exon 11 (60/95, 63.2% ), followed by point mutation (21/95, 23.1% ). Rare internal tandem duplications involving codon 501-502 of exon 9 were found in 2 cases (Ser501-Ala5O2dup, 2/16, 13.5% ). Compared to intestinal GIST, exon 11 mutation was more common in gastric and rectal GIST (P<0.01). Secondary point mutations on exon 17 of KIT were identified in an imatinib-resistant patient (Asp820Val +Tyr823Asp). Conclusion KIT mutations is common in Chinese GIST patients. Mutational status is different in varied primary tumor locations. Secondary mutations of KIT can be found in imatinib-resistant patients. Key words: Gastrointestinal stromal tumor; Gene mutation