Annotation Detail
Information
- Associated Genes
- ALK
- Associated Variants
- ALK p.Phe1245Cys (p.F1245C) ALK p.Phe1245Cys (p.F1245C)
- Associated Disease
- cancer
- Source Database
- CIViC Evidence
- Description
- A Ba/F3 cell line expressing EML4-ALK variant 1 was created, and then exposed to the DNA modifying agent ENU. Cells were subsequently cultured in 96 well plates at increasing concentrations of crizotinib (250, 500, 720, 1000, 1440 and 2000 nM). Cell growth occurred in all wells at 250 nM, and was absent at 2000 nM. From 500 through 1440 nM there were progressively fewer resistant clones present. 422 mutations representing 16 different sites were identified. EML4-ALK F1245C was found at 500 nM crizotinib, and was among the 10 most frequently observed mutations. Ba/F3 cells with unaltered EML4-ALK had crizotinib IC50 values for viability of 132 +/- 45 nM. EML4-ALK F1245C clones from the selection assay had IC50 viability value of 425 +/- 100 nM, while Ba/F3 cells expressing reintroduced EML4-ALK F1245C had IC50 value of 269 +/- 194 nM.
- Variant Origin
- somatic
- Variant Origin
- Somatic
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/1337
- Gene URL
- https://civic.genome.wustl.edu/links/genes/1
- Variant URL
- https://civic.genome.wustl.edu/links/variants/551
- Rating
- 2
- Evidence Type
- Predictive
- Disease
- Cancer
- Evidence Direction
- Supports
- Drug
- Crizotinib
- Evidence Level
- D
- Clinical Significance
- Resistance
- Pubmed
- 22034911
Drugs
| Drug Name | Sensitivity | Supported |
|---|---|---|
| Crizotinib | Resitance or Non-Reponse | true |