Annotation Detail

Information
Associated Genes
ALK
Associated Variants
ALK EML4-ALK V1180L
Associated Disease
lung non-small cell carcinoma
Source Database
CIViC Evidence
Description
Passaging of the alectinib sensitive EML4-ALK containing H3122 NSCLC cell line with increasing levels of alectinib resulted in an alectinib resistant derivative of this cell line named H3122 CHR-A1. A V1180L missense mutation was found in the kinase domain of ALK in H3122 CHR-A1 cells. Both H3122 and H3122 CHR-A1 cells were highly and equally sensitive to ceritinib induced death. In Ba/F3 cells, ectopic expression of EML4-ALK V1180L rendered cells significantly more sensitive to ceritinib than Ba/F3 containing EML4-ALK I1171T mutant (alectinib and crizotinib resistant) or EML4-ALK wt.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/1289
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
Ceritinib
Evidence Level
D
Clinical Significance
Sensitivity/Response
Pubmed
25228534
Drugs
Drug NameSensitivitySupported
CeritinibSensitivitytrue