Annotation Detail
Information
- Associated Genes
- KIT
- Associated Variants
-
KIT p.Thr671Ile (p.T671I)
(
ENST00000412167.7,
ENST00000288135.6,
ENST00000686011.1,
ENST00000687109.1,
ENST00000687246.1,
ENST00000687295.1,
ENST00000689832.1,
ENST00000689994.1,
ENST00000690543.1,
ENST00000692783.1 )
KIT p.Thr671Ile (p.T671I) ( 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 ponatinib and sunitinib sensitizing mutation del 557-558, which induced IL-3 independent growth, and secondary mutation T670I. The cells were tested for Ponatinib and Sunitinib resistances. Ba/F3 cells with del 557-558/T670I mutations (Ponatinib IC50 = 15 +/- 1 nM, Sunitinib IC50 = 12 +/- 2 nM) did not show resistance towards Ponatinib and Sunitinib compared to Ba/F3 cells with del 557-558 alone (Ponatinib IC50 = 3 +/- 0, Sunitinib IC50 = 7 +/- 2 nM). Similarly, patient-derived GIST-T1/670 cells with 560-578 deletion/T670I mutations (Ponatinib IC50 = 8 nM, Sunitinib IC50 = 15 nM) showed no resistance towards Ponatinib and Sunitinib compared to GIST-T1 cells with 560-578 deletion (Ponatinib IC50 = 5 nM, Sunitinib IC50 = 48 nM). Additionally, del 557-558/T670I cells was implanted into mice and treated with Ponatinib or Sunitinib. Ponatinib or Sunitinib were shown to be effective in treating the Ba/F3 mutant cells as tumor volume progressively decreased to zero at around 14 days.
- Variant Origin
- somatic
- Variant Origin
- Somatic
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/7417
- Gene URL
- https://civic.genome.wustl.edu/links/genes/29
- Variant URL
- https://civic.genome.wustl.edu/links/variants/1267
- Rating
- 5
- Evidence Type
- Predictive
- Disease
- Gastrointestinal Stromal Tumor
- Evidence Direction
- Does Not Support
- Drug
- Sunitinib,Ponatinib
- Evidence Level
- D
- Clinical Significance
- Resistance
- Pubmed
- 25239608