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 397 patients with incurable (i.e. metastatic or unresectable) CD117-positive Gastrointestinal stromal tumors (GISTs) examined the relationship between KIT genotype and treatment outcome for patients enrolled in the North American phase III study SWOG S0033/CALGB 150105 who were treated with either 400mg or 800mg of imatinib per day. Of 33 patients with KIT exon-9 mutant GISTs, 31 harbored KIT A502_Y503 internal tandom duplication, one harbored K484_G487del (KHNG). Of the KIT exon 9 mutant patients, 14 were treated with 400mg daily and 19 were treated with 800mg daily. Patients with KIT exon-9 mutant GISTs had a significantly higher response rate when treated with 800mg compared with 400mg (CR/PR 17% vs 67% for 400mg and 800mg, respectively; OR, 9.05; p = .02). However, the authors report that there was not a significant difference in time to progression or overall survival between the two dose groups for patients harboring KIT exon-9 mutant GISTs.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/2477
Gene URL
https://civic.genome.wustl.edu/links/genes/29
Variant URL
https://civic.genome.wustl.edu/links/variants/509
Rating
2
Evidence Type
Predictive
Disease
Gastrointestinal Stromal Tumor
Evidence Direction
Supports
Drug
Imatinib
Evidence Level
B
Clinical Significance
Reduced Sensitivity
Pubmed
18955451
Drugs
Drug NameSensitivitySupported
ImatinibN/Atrue