Annotation Detail

Information
Associated Genes
KIT
Associated Variants
KIT EXON 9 MUTATION
KIT EXON 9 MUTATION
Associated Disease
gastrointestinal stromal tumor
Source Database
CIViC Evidence
Description
This prospective study of 127 patients with metastatic gastrointestinal stromal tumors (GISTs) examined the relationship between KIT genotype and treatment outcome for patients enrolled in a randomized phase II trial of imatinib (CSTI571B 2222). 23 patients harbored KIT exon 9 mutated GISTs: 22 harbored A502_503Ydup and 1 harbored F506_F508dup. Of patients harboring KIT exon 9 mutated GISTs, 11 (47.8%) had a partial response, 6 had stable disease, 4 had progressive disease and 2 were nonassessable. Patients with KIT exon 9 mutant GISTs were significantly more likely to have a partial response than those with WT KIT (P = .013), though significantly less likely than those with KIT exon 11 mutated GISTs (P = .0006). Patients harboring KIT exon 9 mutant GISTs experienced longer event free survival (median: 200 days) than those with WT KIT GISTs (82 days). Furthermore, there was a signficant difference in overall survival between patients with KIT exon 9 mutant and double WT kinase GISTs (P = .0067). There was no significant difference in the rate of treatment failure for patients with exon 9 mutation compared with those with no KIT or PDGFRA mutation (P = .14).
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/2466
Gene URL
https://civic.genome.wustl.edu/links/genes/29
Variant URL
https://civic.genome.wustl.edu/links/variants/509
Rating
3
Evidence Type
Predictive
Disease
Gastrointestinal Stromal Tumor
Evidence Direction
Supports
Drug
Imatinib
Evidence Level
B
Clinical Significance
Sensitivity/Response
Pubmed
14645423
Drugs
Drug NameSensitivitySupported
ImatinibSensitivitytrue