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 variants v1 (E13;A20), v2 (E20;A20), v3a (E6;A20) and v3b (E6ins33;A20) were expressed in Ba/F3 cells using retrovirus. While all constructs rendered Ba/F3 cells IL3-independant, marked differences in sensitivity to ALK inhibitors TAE684 and crizotinib were observed, where v2 was most sensitized to growth inhibition and v3a the least, with v1 and v3b intermediate. While phospho-ALK western blots indicated that the ALK inhibitors acted similarly on both v2 and v3a EML4-ALK variants, blots of cyclohexamide-treated cells showed that v2 had a shorter half-life than 3a in the transduced cells, potentially explaining increased v2 sensitivity. Assays with a panel of mutated EML4-ALK variants of varied length suggested that longer EML4-ALK variants are less stable in cells, although this tendency was not observed across other types of ALK fusion.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/1196
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
Crizotinib
Evidence Level
D
Clinical Significance
Sensitivity/Response
Pubmed
22912387
Drugs
Drug NameSensitivitySupported
CrizotinibSensitivitytrue