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 V1180L mutation in the kinase domain of rearranged ALK was found in an alectinib resistant cell line named H3122 CHR-A1, which was derived from the alectinib sensitive EML4-ALK variant 1 containing NSCLC cell line H3122 by passaging into higher concentrations of alectinib. This cell line is a model for gain of alectinib resistance, and also shows resistance to crizotinib. On the other hand, the often used tool ALK inhibitor TAE684 was highly effective in killing H3122 CHR-A1, where H3122 cells were only slightly more sensitized to TAE684-induced cell death. Ectopic expression of EML4-ALK V1180L in Ba/F3 cells caused IL3 independent growth as well as marked sensitization to TAE684, to a level greater than that seen in EML4-ALK I1171T (alectinib resistance mutation) or EML4-ALK wt, and over 1000x greater sensitivity than unaltered Ba/F3 + IL3.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/1290
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
TAE684
Evidence Level
D
Clinical Significance
Sensitivity/Response
Pubmed
25228534
Drugs
Drug NameSensitivitySupported
TAE684Sensitivitytrue