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
- Several preclinical studies tested the effects of various tyrosine kinase inhibitors (TKIs) on Ba/F3 cell lines with representative primary sunitinib and imatinib sensitizing mutation del 557-558, which induced IL-3 independent growth, and secondary mutation A829P. The cells were tested for Sunitinib and Imatinib resistances. Ba/F3 cells with del 557-558 and A829P mutations did show resistance towards Sunitinib and Imatinib (Sunitinib IC50 for growth inhibition: 319 +- 88 nM and Imatinib IC50: 179 +- 27 nM) compared to Ba/F3 cells with the del 557-558 mutation (Sunitinib IC50: 7 +- 2 nM and Imatinib IC50: 27 +- 8 nM). Imatinib and Sunitinib were shown to not reduce p-KIT at all in Ba/F3 cells with del 557-558/ A829P mutations. Patient-derived GIST-T1/829 cells with 560-578 deletion/A829P mutations (Sunitinib IC50: 1168 nM and Imatinib IC50:1201 nM) did show resistance towards Sunitinib and Imatinib compared to GIST-T1 cells with 560-578 deletion alone (Sunitinib IC50: 15 nM and Imatinib IC50: 30 nM). Sunitinib and Imatinib did not inhibit p-KIT, p-ERK, and p-AKT in GIST-T1/829 cells.
- Variant Origin
- somatic
- Variant Origin
- Somatic
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/7415
- 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
- Supports
- Drug
- Sunitinib,Imatinib
- Evidence Level
- D
- Clinical Significance
- Resistance
- Pubmed
- 25239608