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 implication of 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 amplification and direct sequencing. Clinicopathologic characteristics were correlated to gene mutations.
Results: Of the 141 tumors studied, approximately 76.6% had KIT gene mutations, 2.8% had PDGFRA gene mutations and 20.6% had a wild-type 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 in exons 17. The most frequent sites of mutation were in exon 11 and the mutations 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 (chi(2) = 6.728, P = 0.009; chi(2) = 4.059, P = 0.044), however, mutation rate on exon 11 was significantly increased in gastric stromal tumor (chi(2) = 5.713, P = 0.017; chi(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 patients with or without gene mutations.
Conclusion: KIT and PDGFRA gene were frequently found in patients with GISTs. Gene mutation rate varies in originated organ.