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 G1269A mutation was tested for sensitivity to ceritinib via transduction into Ba/F3 cells and generation of survival curves varying ceritinib concentration. IC50 of 33 nM was seen, which was 1.5 times the IC50 for EML4-ALK wild-type, indicating sensitivity of the G1269A mutation to ceritinib in the context of EML4-ALK. The mutation was also tested for ceritinib sensitivity in the context of NPM-ALK, where IC50 values were reported of 19 nM and 20 nM for mutant and wild-type versions, respectively, also indicating sensitivity. In western blots, Y1604 pALK levels for wild-type NPM-ALK were ablated at 100 nM, while at 100 nM residual pALK levels were seen in G1269A blotting, with ablation of signal at and above 300 nM, which differed somewhat from the equivalent IC50 values reported for mutant and wild-type in the NPM-ALK background, but still agrees with sensitivity to ceritinib for this mutation.
- Variant Origin
- somatic
- Variant Origin
- Somatic
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/1355
- 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
- Ceritinib
- Evidence Level
- D
- Clinical Significance
- Sensitivity/Response
- Pubmed
- 25727400
Drugs
| Drug Name | Sensitivity | Supported |
|---|---|---|
| Ceritinib | Sensitivity | true |