Annotation Detail
Information
- Associated Genes
- ALK
- Associated Variants
- ALK EML4-ALK E20;A20
- Associated Disease
- lung non-small cell carcinoma
- Source Database
- CIViC Evidence
- Description
- EML4-ALK fusions occur in 2-7% of lung adenocarcinomas. Transduction of Ba/F3 cells with EML4-ALK variant 2 (EML4 exon 20 fused to ALK exon 20) caused the cells to grow independently of IL3 addition. EML4-ALK may be a client protein of Hsp90. Addition of Hsp90 inhibitor 17-DMAG to the EML4-ALK variant 2 cells induced cell death which was rescued at lower 17-DMAG concentrations by IL3 addition. This result suggests that 17-DMAG specifically targeted the EML4-ALK driver in these cells. Finally, 17-DMAG and crizotinib showed a synergistic effect in killing EML4-ALK variant 2 cells.
- Variant Origin
- somatic
- Variant Origin
- Somatic
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/1204
- Gene URL
- https://civic.genome.wustl.edu/links/genes/1
- Variant URL
- https://civic.genome.wustl.edu/links/variants/500
- Rating
- 2
- Evidence Type
- Predictive
- Disease
- Lung Non-small Cell Carcinoma
- Evidence Direction
- Supports
- Drug
- Alvespimycin,Crizotinib
- Evidence Level
- D
- Clinical Significance
- Sensitivity/Response
- Pubmed
- 22912387
Drugs
| Drug Name | Sensitivity | Supported |
|---|---|---|
| Alvespimycin | Sensitivity | true |
| Crizotinib | Sensitivity | true |