Annotation Detail
Information
- Associated Genes
- KIT
- Associated Variants
-
KIT p.Ala830Pro (p.A830P)
(
ENST00000288135.6,
ENST00000412167.7,
ENST00000686011.1,
ENST00000687109.1,
ENST00000687246.1,
ENST00000687295.1,
ENST00000689832.1,
ENST00000689994.1,
ENST00000690543.1,
ENST00000692783.1 )
KIT p.Ala830Pro (p.A830P) ( 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
- Ponatinib possesses potent activity against A829P KIT mutant cells in preclinical experiments. A preclinical study tested the effect of a tyrosine kinase inhibitor (TKI) on Ba/F3 cell lines with representative primary ponatinib-sensitizing mutation del 557-558, which induced IL-3 independent growth, and secondary mutation A829P. The cells were tested for Ponatinib resistance. Ba/F3 cells with del 557-558 and A829P mutations (IC50 for growth inhibition: 2 nM) did not show resistance towards Ponatinib compared to Ba/F3 cells with the del 557-558 mutation alone (IC50: 3 nM). Ponatinib was shown to inhibit KIT phosphorylation in moderate concentrations. Similarly, GIST-T1/829 cells with 560-578 deletion/A829P mutations (IC50 = 16 nM) were not resistant to Ponatinib compared to GIST T1 cells with 560-578 deletion alone (IC50 = 5 nM). Ponatinib inhibited phosphorylation in KIT, ERK, and AKT at moderate to high concentrations in GIST-T1/829 cells.
- Variant Origin
- somatic
- Variant Origin
- Somatic
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/7413
- Gene URL
- https://civic.genome.wustl.edu/links/genes/29
- Variant URL
- https://civic.genome.wustl.edu/links/variants/990
- 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 |