Molecular epidemiology of gastrointestinal stromal tumors (GISTs): comparison of North and South American patient populations.

22142 Background: KIT or PDGFRA mutations are found in 80-90% of gastrointestinal stromal tumors (GIST) arising in North American, western European, or Asian populations.,To compare kinase genotypes of GIST tumors obtained from Argentinian patients to those obtained from North American patients (pts).,302 Argentinian (ARG) pts with a histological diagnosis of GIST were included in a prospective clinical database (Grupo Argentino de Tumores del Estroma Gastrointestinal- Digestivos). Paraffin blocks of tissue from 97 of these pts were analyzed using high performance liquid chromatography (HPLC) and DNA sequencing for KIT (exon 9, 11, 13, 17) and PDGFRA gene mutations (exons 12, 14, 18). The ARG genotyping results were compared to our previously genotyped group of 1354 North American pts (NA).,GIST mutations were found in 83.8% and 82.5% of NA and ARG GISTs, respectively. 1027 NA (75.8%) and 70 ARG (72%) patients had KIT gene mutations-exon 11 was mutated 63% and 65% of cases, respectively. There was a slightly greater frequency of PDGFRA gene mutations in the ARG group (8.05 vs. 10.5%). The percentage of wild-type GISTs was similar between the two populations (16.2% NA and 17.5% ARG). Overall, there was no statistically significance in the spectrum or frequency of NA and ARG GIST mutations. Clinical response data (RECIST) was available for 24 pts with exon 11-mutant GIST and 6 patients with wild-type GIST treated with imatinib (IM) for advanced disease. CR/PR was observed in 42% of IM-treated patients with exon 11-mutant GIST compared with 17% of patients with WT-GISTs. The clinical benefit rate (CR+PR+SD) of IM was 100% for patients with exon 11-mutant GIST. Ongoing studies will further correlate clinical features with molecular genotype in the ARG patients (e.g. post-resection recurrence risk; progression-free and overall survival during IM therapy). In addition, analysis of a cohort of ARG pediatric GIST patients is underway.,molecular epidemiology of GISTs appears similar between ARG and NA populations. [Table: see text].