Acquired cis-mutations in the ATP-binding domain (encoded by exon 13 or 14 of KIT and exon 14 of PDGFRA) or activation loop (encoded by exon 17 of KIT and exon 18 of PDGFRA) are the main causes of secondary resistance to KIT-mutant and PDGFRA-mutant GIST (52). The gene discussed is PDGFRA; the disease is gastrointestinal stromal tumor.