Annotation Detail
Information
- Associated Genes
- KIT
- Associated Variants
-
KIT p.Lys643Glu (p.K643E)
(
ENST00000288135.6,
ENST00000412167.7,
ENST00000686011.1,
ENST00000687109.1,
ENST00000687246.1,
ENST00000687295.1,
ENST00000689832.1,
ENST00000689994.1,
ENST00000690543.1,
ENST00000692783.1 )
KIT p.Lys643Glu (p.K643E) ( ENST00000288135.6, ENST00000412167.7, ENST00000686011.1, ENST00000687109.1, ENST00000687246.1, ENST00000687295.1, ENST00000689832.1, ENST00000689994.1, ENST00000690543.1, ENST00000692783.1 ) - Associated Disease
- gastrointestinal stromal tumor
- Source Database
- CIViC Evidence
- Description
- The GIST882 patient derived cell line expressing KIT K642E mutation demonstrated sensitivity to ponatinib (IC50: 31nmol/L) and sunitinib (IC50: 54nmol/L) treatments. In comparison, the insensitve KIT-independent GIST226 cell line showed IC50 >2807nmol/L and >5000nmol/L for these drugs respectively. IC50 was determined by assessing cell viability. The GIST882 cell line only showed reduced levels of phospho-KIT and phospho-ERK at high concentrations for ponatinib and sunitinib, while phospho-AKT levels were reduced at all concentrations for ponatinib and sunitinib.
- Variant Origin
- somatic
- Variant Origin
- Somatic
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/7397
- Gene URL
- https://civic.genome.wustl.edu/links/genes/29
- Variant URL
- https://civic.genome.wustl.edu/links/variants/978
- Rating
- 3
- Evidence Type
- Predictive
- Disease
- Gastrointestinal Stromal Tumor
- Evidence Direction
- Supports
- Drug
- Ponatinib,Sunitinib
- Evidence Level
- D
- Clinical Significance
- Sensitivity/Response
- Pubmed
- 25239608