KIT and PDGFRalpha mutations in 104 patients with gastrointestinal stromal tumors (GISTs): a population-based study.

Background: The prognostic significance of KIT or platelet-derived growth factor receptor alpha (PDGFR alpha) mutations in gastrointestinal stromal tumors (GISTs) is still controversial. Patients and methods: In all, 104 patients were diagnosed with GISTs by KIT immunoreactivity; tumor DNA was sequenced for the presence of mutations in KIT exons 9, 11, 13 and 17 and in PDGFR alpha exons 12 and 18. Disease-free survival (DFS) was analyzed in 85 radically resected patients. Results: KIT mutations occurred in exon 11 (69), in exon 9 (11) and in exon 17 (1). PDGFR alpha mutations were detected in exon 18 (10) and in exon 12 (3). Ten GISTs were wild type. Exon 11 mutations were as follows: deletions in 42 cases and point mutations in 20 cases and insertions and duplications, respectively, in 2 and 5 cases. A better trend in DFS was evident for duplicated and point-mutated exon 11 KIT GISTs. There was a significant association between PDGFR alpha mutations, gastric location and lower mitotic index. Moreover, PDGFR alpha-mutated GISTs seemed to have a better outcome. Conclusions: Point mutations and duplications in KIT exon 11 are associated with a better clinical trend in DFS. PDGFR alpha-mutated GISTs are preferentially localized in the stomach and seem to have a favorable clinical behavior.