Annotation Detail
Information
- Associated Genes
- KIT
- Associated Variants
-
KIT p.Asp817Glu (p.D817E)
(
ENST00000288135.6,
ENST00000412167.7,
ENST00000686011.1,
ENST00000687109.1,
ENST00000687246.1,
ENST00000687295.1,
ENST00000689832.1,
ENST00000689994.1,
ENST00000690543.1,
ENST00000692783.1 )
KIT p.Asp817Glu (p.D817E) ( 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
- A preclinical study was done in order to test the effects of a tyrosine kinase inhibitor (TKI) on the ponatinib-sensitive KIT-mutant cell line GIST-T1 derived from Gastrointestinal Stromal Tumor (GIST) patients with primary mutation 560-578 deletion and additional secondary mutation D816E. The cells were tested for Ponatinib resistance. GIST-T1/816 cells containing del 560-578 and D816E mutations (IC50: 23 nM) did not show resistance towards Ponatinib compared to GIST-T1 cells with only del 560-578 mutation (IC50: 5 nM). Ponatinib reduced phosphorylation in KIT, AKT, and ERK at higher concentrations. According to the results, the authors suggest that Ponatinib remained highly active in GIST cell lines with secondary mutation D816E.
- Variant Origin
- somatic
- Variant Origin
- Somatic
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/7401
- Gene URL
- https://civic.genome.wustl.edu/links/genes/29
- Variant URL
- https://civic.genome.wustl.edu/links/variants/1559
- Rating
- 4
- Evidence Type
- Predictive
- Disease
- Gastrointestinal Stromal Tumor
- Evidence Direction
- Does Not Support
- Drug
- Ponatinib
- Evidence Level
- D
- Clinical Significance
- Resistance
- Pubmed
- 25239608
Drugs
| Drug Name | Sensitivity | Supported |
|---|---|---|
| Ponatinib | Resitance or Non-Reponse | false |