Annotation Detail
Information
- Associated Genes
- ALK
- Associated Variants
- ALK EML4-ALK V1180L
- Associated Disease
- lung non-small cell carcinoma
- Source Database
- CIViC Evidence
- Description
- The EML4 ALK variant 1 containing NSCLC cell line H3122 is highly sensitive to alectinib, and an alectinib resistant derivative cell line H3122 CHR-A1 was generated by incubation of H3122 in increasing levels of alectinib culminating in 1 micro-molar, over a course of 7 months. The ALK kinase domain mutation V1180L was found in these cells, and Ba/F3 cells expressing EML4 ALK V1180L were highly resistant to alectinib. Simulations indicated that the V1180L mutation interfered with alectinib binding. The V1180L mutation was found to be more resistant to alectinib than the I1171T mutation found in an ALK-positive NSCLC patient who developed alectinib resistance on lower dose alectinib (300mg twice daily).
- Variant Origin
- somatic
- Variant Origin
- Somatic
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/1286
- Gene URL
- https://civic.genome.wustl.edu/links/genes/1
- Variant URL
- https://civic.genome.wustl.edu/links/variants/528
- Rating
- 3
- Evidence Type
- Predictive
- Disease
- Lung Non-small Cell Carcinoma
- Evidence Direction
- Supports
- Drug
- Alectinib
- Evidence Level
- D
- Clinical Significance
- Resistance
- Pubmed
- 25228534
Drugs
| Drug Name | Sensitivity | Supported |
|---|---|---|
| Alectinib | Resitance or Non-Reponse | true |