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 mutation was tested for sensitivity to alectinib using Ba/F3 cells. In Ba/F3 cells with ectopic EML4-ALK variant 1 G1269A, IC50 of 84 nM was reported with alectinib, which was a 6 fold increase over IC50 for EML4-ALK wild-type. The authors considered a fold difference of 4 to 10 between the alectinib-sensitized wild-type and mutant variant to indicate a resistant mutant variant. In the background of the NPM-ALK fusion, IC50 for G1269A mutation was 104 nM, which was 5.3 fold that reported for NPM-ALK wild-type. Western blots of alectinib treated NPM-ALK G1269A were performed and reduced pALK Y1604 was seen at 300 nM alectinib, and no pALK at 1000 nM. In contrast pALK signal was ablated at and above 100 nM in NPM-ALK wild-type.
- Variant Origin
- somatic
- Variant Origin
- Somatic
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/1354
- Gene URL
- https://civic.genome.wustl.edu/links/genes/1
- Variant URL
- https://civic.genome.wustl.edu/links/variants/552
- Rating
- 3
- Evidence Type
- Predictive
- Disease
- Cancer
- Evidence Direction
- Supports
- Drug
- Alectinib
- Evidence Level
- D
- Clinical Significance
- Resistance
- Pubmed
- 25727400
Drugs
| Drug Name | Sensitivity | Supported |
|---|---|---|
| Alectinib | Resitance or Non-Reponse | true |