Annotation Detail
Information
- Associated Genes
- ALK
- Associated Variants
- ALK p.Gly1202Arg (p.G1202R) ALK p.Gly1202Arg (p.G1202R)
- Associated Disease
- cancer
- Source Database
- CIViC Evidence
- Description
- This study compared drug responses in Ba/F3 cells expressing either EML4-ALK or NPM-ALK fusions, with or without G1202R ALK mutation. Cells expressing the EML4-ALK variant 3 with G1202R ALK mutation were more resistant to brigatinib treatment (IC50 325 nM) than cells expressing wildtype EML4-ALK variant 3 (IC50 6 nM). These same experiments performed with the NPM-ALK fusion resulted in IC50 of 149 nM for G1202R and 11nM for wild type, consistent with resistance. In Western blots, ablation of pALK with brigatinib treatment above 100 nM was seen in Ba/F3 cells expressing NPM-ALK wildtype, but remained apparent at 1000 nM brigatinib in NPM-ALK G1202R cells, despite dose-dependent reduction.
- Variant Origin
- somatic
- Variant Origin
- Somatic
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/1351
- Gene URL
- https://civic.genome.wustl.edu/links/genes/1
- Variant URL
- https://civic.genome.wustl.edu/links/variants/171
- Rating
- 3
- Evidence Type
- Predictive
- Disease
- Cancer
- Evidence Direction
- Supports
- Drug
- Brigatinib
- Evidence Level
- D
- Clinical Significance
- Resistance
- Pubmed
- 25727400
Drugs
| Drug Name | Sensitivity | Supported |
|---|---|---|
| Brigatinib | Resitance or Non-Reponse | true |