Table 1.
Genotype | Features |
---|---|
KIT mutations (75–80 % of sporadic GISTs) | |
Exon 11 | Most common mutation in sporadic GISTs (65–70 %); present in tumors localized at all gastrointestinal sites; best response to imatinib; also reported in familial GISTs |
Exon 9 | More common in GISTs originating from the small bowel/colon; intermediate/dose-dependent response to imatinib in advanced GISTs |
Exon 13 | Present in tumors localized at all gastrointestinal sites; observed clinical responses to imatinib; reported in familial GISTs; more often as secondary mutations in imatinib-resistant tumors |
Exon 17 | Present in tumors localized at all gastrointestinal sites; observed clinical responses to imatinib (except for p.D816V); reported in familial GISTs; more often as secondary mutations in imatinib-resistant tumors |
PDGFRA mutations (5–13 % of sporadic GISTs) | |
Exon 12 | Present in tumors localized at all gastrointestinal sites; observed clinical responses to imatinib |
Exon 14 | Only a few cases described in the literature; more common in GISTs originating from the stomach |
Exon 18 | More common in GISTs originating from the stomach, usually with epithelioid morphology; often related to indolent clinical behavior; p.D842V is the most common and is resistant to imatinib; other exon 18 mutations are sensitive to imatinib |
KIT/PDGFRA wild type | Frequent in pediatric GISTs; poor response to imatinib; typical for GISTs related to neurofibromatosis type 1, Carney’s triad (gastric GIST + pulmonary chondroma ± paraganglioma), or Carney-Stratakis syndrome (GIST + paraganglioma, characterized by mutations in genes encoding SDH subunits SDHA, SDHB, SDHC, SDHD), and/or IGF1R expression |
IGF1R insulin-like growth factor 1 receptor, SDH succinate dehydrogenase