Annotation Detail
Information
- Associated Genes
- ALK
- Associated Variants
- ALK EML4-ALK C1156Y
- Associated Disease
- lung non-small cell carcinoma
- Source Database
- CIViC Evidence
- Description
- EML4-ALK variant 3 containing NSCLC cell line H2228 xenografts in SCID beige mice were treated with increasing doses of crizotinib up to 100 mg/kg per day by oral gavage. At approximately 40 days tumors progressed. 80 progressed tumors were tested for ALK mutations, and 6 mutant ALK variants were found. Two of the mutations were at ALK C1156Y. In Ba/F3 cells, EML4-ALK variant 3 with C1156Y was introduced and tested for crizotinib sensitivity. Survival IC50 value of 177 nM was reported, which is 9.3 times the IC50 reported for crizotinib in EML4-ALK wild-type Ba/F3 cells.
- Variant Origin
- somatic
- Variant Origin
- Somatic
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/1346
- Gene URL
- https://civic.genome.wustl.edu/links/genes/1
- Variant URL
- https://civic.genome.wustl.edu/links/variants/6
- Rating
- 4
- Evidence Type
- Predictive
- Disease
- Lung Non-small Cell Carcinoma
- Evidence Direction
- Supports
- Drug
- Crizotinib
- Evidence Level
- D
- Clinical Significance
- Resistance
- Pubmed
- 24675041
Drugs
| Drug Name | Sensitivity | Supported |
|---|---|---|
| Crizotinib | Resitance or Non-Reponse | true |