Annotation Detail

Information
Associated Genes
KIT
Associated Variants
KIT EXON 11 MUTATION
KIT EXON 11 MUTATION
Associated Disease
gastrointestinal stromal tumor
Source Database
CIViC Evidence
Description
This prospective study of 127 pretreatment patients with metastatic gastrointestinal stromal tumors (GISTs) examined the relationship between kinase (KIT and PDGFRA) genotype and treatment outcome for patients enrolled in a randomized phase II trial of imatinib (CSTI571B 2222). 85 patients harbored KIT exon 11 mutated GISTs: 71 had an in-frame deletion and 15 had unspecified point mutations (3 codon 557 cases, 3 codon 559 cases, 6 codon 560 cases and 2 codon 576 cases). Of patients harboring KIT exon 11 mutated GISTs, 71 (83.5%) had a partial response, 7 had stable disease, 4 had progressive disease and 3 were nonassessable. Patients with KIT exon 11 mutations were significantly more likely to have a partial response than those with KIT exon 9 mutations (P=.0006) or double WT kinases (WT KIT and WT PDGFRA; P < .0001). The presence of a KIT exon 11 mutation was the strongest predictor of response (Hazard ratio= 7.85). Patients harboring KIT exon 11 mutant GISTs experienced longer event free survival (median: 687 days) than those with KIT exon 9 mutant or double WT kinase GISTs (200 days and 82 days, respectively). Furthermore, patients whose tumors expressed an exon 11 mutant KIT had improved overall survival compared to patients whose tumor expressed an exon 9 mutant KIT (P = .0034) or double WT kinases (P <.0001).
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/654
Gene URL
https://civic.genome.wustl.edu/links/genes/29
Variant URL
https://civic.genome.wustl.edu/links/variants/66
Rating
4
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