Spectrum and prognostication of KIT and PDGFRA mutation in gastrointestinal stromal tumors

Recent studies reported various mutation rates in gastrointestinal stromal tumors (GISTs) and inconsistent prognostic value of mutation in GIST patients. Our purpose was to analyze the frequency and spectrum of KIT and PDFGRA in a large series study and to determine if the presence of mutation and mutation type serve as prognostic factors in GIST patients.

A total of 134 GISTs were subjected to mutation analysis of KIT (exons 9, 11, 13, and 17) and PDGFRA (exons 10, 12, 14, and 18). Clinicopathologic characteristics and survivals were correlated to KIT mutation.

Approximately 69% of GISTs had KIT/PDGFRA mutation in Taiwanese GIST patients, with 99% of mutations occurred in KIT and 1% occurred in PDGFRA. Mutation rate was significantly increased in GISTs with mitotic counts >5 per 50 high power fields (chi(2) test, p=0.045). However, KIT mutations, regardless of the location (exons 9 versus 11) and type (missense, insertion, and deletion, including deletion specifically involving codons 557 and 558) of mutation, were not significantly associated with poor progression-free survivals. Comparing the overall survival in imatinib-treated patients, there was no significant difference between patients with exon 11 mutation and those with exon 9 mutation (p=0.473).

GISTs were commonly associated with KIT mutation, but rarely associated with PDGFRA mutation in Taiwan. The presence of KIT mutation and mutation type was not significant prognostic factors in GIST patients without imatinib treatment, suggesting that there is no need to stratify GIST patients by mutation status in clinical trials of targeted therapy.