Annotation Detail
Information
- Associated Genes
- ALK
- Associated Variants
- ALK p.Gly1202Arg (p.G1202R) ALK p.Gly1202Arg (p.G1202R)
- Associated Disease
- lung non-small cell carcinoma
- Source Database
- CIViC Evidence
- Description
- Ba/F3 cells expressing EML4-ALK variant 1 with ALK G1202R mutation were assessed for ceritinib sensitivity. Crizotinib was shown to confer significantly more potency than ceritinib (43-fold decrease in IC50). EML4-ALK variant 3 NSCLC cell line H2228 was used in SCID mouse xenografts which were exposed to increasing crizotinib up to 100 mg/kg. Within 40 days tumors progressed, and progressed tumors were assayed for ALK mutation. Of 80 tumors, 6 had ALK mutation and 3 of these were G1202R. Treatment of crizotinib progressed tumors with ceritinib resulted in tumor growth which did not differ appreciably from crizotinib or vehicle treatment of these tumors.
- Variant Origin
- somatic
- Variant Origin
- Somatic
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/1345
- Gene URL
- https://civic.genome.wustl.edu/links/genes/1
- Variant URL
- https://civic.genome.wustl.edu/links/variants/171
- Rating
- 4
- Evidence Type
- Predictive
- Disease
- Lung Non-small Cell Carcinoma
- Evidence Direction
- Supports
- Drug
- Ceritinib
- Evidence Level
- D
- Clinical Significance
- Resistance
- Pubmed
- 24675041
Drugs
| Drug Name | Sensitivity | Supported |
|---|---|---|
| Ceritinib | Resitance or Non-Reponse | true |