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This study found that most gastrointestinal stromal tumours without KIT mutations instead carry activating mutations in the related receptor PDGFRA, including the D842V mutation that resists imatinib, completing the genetic definition of the disease.
Mutation analysis of KIT-wild-type gastrointestinal stromal tumours identifying activating PDGFRA mutations in about a third, mutually exclusive with KIT mutations, with the mutant receptors showing constitutive activation and, for D842V, resistance to imatinib in vitro, while other PDGFRA mutants were sensitive.
PDGFRA testing is part of standard GIST genotyping, and the imatinib resistance of D842V predicted here led to the development of avapritinib.