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
- A preclinical study tested the effects of a tyrosine kinase inhibitor (TKI) on Ba/F3 cell lines with representative primary imatinib-sensitizing mutation del 557-558, which induced IL-3 independent growth, and secondary mutation T670I. The cells were tested for Imatinib resistance. Ba/F3 cells with del 557-558/T670I mutations (IC50 = >10000 nM) showed resistance towards Imatinib compared to Ba/F3 cells with del 557-558 alone (IC50 = 27 +- 8 nM). Similarly, patient-derived GIST-T1/670 cells with 560-578 deletion/T670I mutations (IC50 > 5000 nM) did show resistance towards Imatinib compared to GIST-T1 cells with 560-578 deletion (IC50 = 30 nM). Del 557-558/T670I cells were implanted into mice and treated with Imatinib. Imatinib was not effective in treating the del 557-558/T670I cells in mice as tumor volume progressively increased. In addition, Ba/F3 cells were mutagenized with N-ethyl-N-nitrosourea and incubated with varying concentrations of Imatinib. In Imatinib incubated cells, T670I mutations were seen in approximately 80% of the resistant cell populations.
- Variant Origin
- somatic
- Variant Origin
- Somatic
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/7416
- 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
- Supports
- Drug
- Imatinib
- Evidence Level
- D
- Clinical Significance
- Resistance
- Pubmed
- 25239608
Drugs
| Drug Name | Sensitivity | Supported |
|---|---|---|
| Imatinib | Resitance or Non-Reponse | true |