The analysis of status and clinical implication of KIT and PDGFRA mutations in gastrointestinal stromal tumor (GIST)

Background and objective: to analyze the frequency and spectrum of KIT and platelet-derived growth factor receptor-alpha (PDGFRA) gene in a large series of study and to explore the clinical clinical implication mutations in the gastrointestinal stromal tumors (GISTs) in China. Method: A total of 141 GISTs were subject to mutation analysis of KIT (exons 9, 11, 13, and 17) and PDGFRA (exons 12 and 18) using PCR amplication and direct sequencing. Clinicopathologic characteristics were correlated to gene mutations. Results: Of the 141 studied, approximately 76.6% had KIT gene mutations, 2.8% had PDGFRA gene mutations and 20.6% had it wildtype gene of KIT and PDGFRA. Among those with KIT gene mutations, 70.2% occurred in exon 11.5.7% in exon 9,0.7% in exon 13. and no Mutation was detected ill exons 17.The most frequent sites of mutation were in excon II and the mutation clustered in the classic "hot spot" at the 5'end of the exon mostly heterogeneous and the second "hot spot" were internal tandem duplications (ITD) at the 3'end of the exon. The overall mutation rate was significantly lower in GISTs originated from colorectum or extra-gastrointestinal tract (%(2) = 6.728, P= 0.009; %(2) = % (2) =4.059. P = 0.044), however, mutation rate on xon 11 significantly increased in gastric stormal tumor (%(2) = 5.713, P=0.017; %(2) = 4.341, P = 0.037) There were no significant differences in terms of age, gender. tumor size. mitotic counts, grade of malignant potential and liver metastasis in patient with or without gene mutations. Conclusion: KIT and PDGFRA gene frequently found in patients with GISTs. Gene mutation rate varies in originated organ.