Annotation Detail
Information
- Associated Genes
- ALK
- Associated Variants
- ALK p.Gly1269Ala (p.G1269A) ALK p.Gly1269Ala (p.G1269A)
- Associated Disease
- cancer
- Source Database
- CIViC Evidence
- Description
- EML4-ALK with ALK G1269A has been seen in crizotinib resistant NSCLC, and this mutation was tested for Brigatinib sensitivity via ectopic expression in Ba/F3 cells, where half maximal inhibitory concentration of 9 nM was seen, which was 1.5 times the IC50 of EML4-ALK wild-type to brigatinib. NPM-ALK G1269A was also tested for brigatinib sensitivity, and IC50 values of 11 nM were reported for both NPM-ALK G1269A and NPM-ALK wild-type. In western blotting, brigatinib at and above 100 nM ablated pALK signal (Y 1604), indicating sensitivity of this variant to brigatinib together with the other results.
- Variant Origin
- somatic
- Variant Origin
- Somatic
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/1353
- Gene URL
- https://civic.genome.wustl.edu/links/genes/1
- Variant URL
- https://civic.genome.wustl.edu/links/variants/552
- Rating
- 2
- Evidence Type
- Predictive
- Disease
- Cancer
- Evidence Direction
- Supports
- Drug
- Brigatinib
- Evidence Level
- D
- Clinical Significance
- Sensitivity/Response
- Pubmed
- 25727400
Drugs
| Drug Name | Sensitivity | Supported |
|---|---|---|
| Brigatinib | Sensitivity | true |