Annotation Detail
Information
- Associated Genes
- KIT
- Associated Variants
-
KIT p.Asn823Lys (p.N823K)
(
ENST00000288135.6,
ENST00000412167.7,
ENST00000686011.1,
ENST00000687246.1,
ENST00000687109.1,
ENST00000687295.1,
ENST00000689832.1,
ENST00000689994.1,
ENST00000690543.1,
ENST00000692783.1 )
KIT p.Asn823Lys (p.N823K) ( 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 primary TKI-sensitizing del 557-558 mutation, which induced IL-3 independent growth, and secondary mutation N822K. The cells were tested for Sunitinib and Imatinib resistances. Ba/F3 cells with del 557-558 and N822K mutations (Sunitinib IC50 for growth inhibition: 225 +- 19 nM, Imatinib IC50: 483 +- 24 nM) did show resistance towards Sunitinib and Imatinib compared to Ba/F3 cells with the del 557-558 alone (Sunitinib IC50: 7 +- 2 nM, Imatinib IC50: 27 +- 8 nM). Sunitinib and Imatinib did not completely inhibit KIT phosphorylation at 1000 nM, which was the highest concentration tested. Additionally, Ba/F3 cells were mutagenized with N-ethyl-N-nitrosourea and incubated with varying concentrations of Sunitinib and Imatinib separately. From these results, N822K mutations were the most frequent KIT mutation observed in resistant Ba/F3 cell populations incubated in Sunitinib. In Imatinib incubated cells, N822K mutations were seen in approximately 10% of resistant Ba/F3 cell clones.
- Variant Origin
- somatic
- Variant Origin
- Somatic
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/7414
- Gene URL
- https://civic.genome.wustl.edu/links/genes/29
- Variant URL
- https://civic.genome.wustl.edu/links/variants/1263
- Rating
- 4
- Evidence Type
- Predictive
- Disease
- Gastrointestinal Stromal Tumor
- Evidence Direction
- Supports
- Drug
- Imatinib,Sunitinib
- Evidence Level
- D
- Clinical Significance
- Resistance
- Pubmed
- 25239608