Annotation Detail

Information
Associated Genes
KIT
Associated Variants
KIT V560_L576DEL
KIT V560_L576DEL
Associated Disease
gastrointestinal stromal tumor
Source Database
CIViC Evidence
Description
In the patient-derived cell line GIST430 harboring KIT V560_L576del primary activating mutation implanted in mice, imatinib and ponatinib were shown to reduce KIT phosphorylation compared to the vehicle. In GIST430 cell lines, ponatinib and imatinib reduced phospho-AKT and phospho-ERK levels. A cell line derived from GIST430 patients expressing KIT V560_L576del primary mutation demonstrated sensitivity to imatinib (IC50: 61nmol/L) and ponatinib (IC50: 12nmol/L) treatments. In comparison, the insensitve KIT-independent GIST226 cell line showed IC50 >5000nmol/L and 2807nmol/L for these drugs respectively. IC50 was determined by assessing cell viability.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/7393
Gene URL
https://civic.genome.wustl.edu/links/genes/29
Variant URL
https://civic.genome.wustl.edu/links/variants/1550
Rating
4
Evidence Type
Predictive
Disease
Gastrointestinal Stromal Tumor
Evidence Direction
Does Not Support
Drug
Imatinib,Ponatinib
Evidence Level
D
Clinical Significance
Sensitivity/Response
Pubmed
25239608
Drugs
Drug NameSensitivitySupported
ImatinibSensitivityfalse
PonatinibSensitivityfalse