While a majority of GISTs (~80%) are driven by gain-of-function mutations in the proto-oncogene KIT on chromosome 4q11-21 (Hirota et al., 1998; Kindblom et al., 1998; Sommer et al., 2003; Rubin et al., 2005), about 20% of GIST lack KIT mutations but either carrying gain-of-function mutations of the KIT homolog platelet-derived growth factor receptor alpha (PDGFRA), or wildtype for both genes. The gene discussed is PDGFRA; the disease is gastrointestinal stromal tumor.