Abstract

Background: About 80–90% of gastrointestinal stromal tumor (GIST) patients harbor KIT proto-oncogene (KIT) and/or platelet-derived growth factor receptor alpha (PDGFRA) gain-of-function mutations. The KIT gene also encodes a tyrosine kinase receptor; therefore, KIT/PDGFRA alterations not only serve as hallmarks, but also as potential therapeutic targets. Previous reports have demonstrated that differences in the KIT/PDGFRA mutation rates are generally attributed to ethnic and/or technical factors. Herein, we report a molecular profiling of KIT/PDGFRA in a Latin American cohort of GIST patients. Methods: In this observational study, DNA samples were obtained from paraffin blocks in 42 GIST patients. We performed KIT/PDGFRA molecular profiling by Sanger sequencing. Patients’ clinical characteristics were obtained from their medical records. A single case was further analyzed with next-generation sequencing (NGS). Results: Patients were predominantly females (n=22; 52.4%). Median age at diagnosis was 53 years old. As expected, the stomach was the most frequent primary location (47.6%), and 38.1% of cases were metastatic. We detected KIT and PDGFRA alterations in 64.3% and 4.8% of patients, respectively. Within this subset (n=29), 82.8% had exon-11 KIT mutations, and 6.9% had exon 18 PDGFRA mutations. As predicted, KIT and PDGFRA mutations were mutually exclusive, and 31% (n=13) were wild-type KIT/PDGFRA. These results could be attributed to ethnic and methodological differences. Therefore, we presented a case of a metastatic patient analyzed by NGS to illustrate the clinical utility of an alternative screening strategy to Sanger sequencing. Conclusions: There were a high proportion of wild-type GISTs in this cohort. This could be attributed to technical/methodological and/or ethnic/genetic differences. Our findings also encourage the use of alternative techniques, such as NGS for KIT/PDGFRA screenings, particularly in the case of advanced-stage patients.