Annotation Detail

Information
Associated Genes
ALK
Associated Variants
ALK EML4-ALK V1180L
Associated Disease
lung non-small cell carcinoma
Source Database
CIViC Evidence
Description
ALK mutation V1180L was found in an H3122 derivative cell line that had become alectinib resistant after being passaged in increasing levels of alectinib. EML4-ALK V1180L and EML4-ALK wild-type were ectopically expressed in Ba/F3 cells, and brigatinib showed strong activity against both variants. The IC50 for brigatinib against EML4-ALK wild-type was 0.95, which is about 3x higher than the IC50 that was observed for alectinib, but about 6x lower than that for crizotinib. In contrast, the IC50 for brigatinib against the alectinib resistance variant EML4-ALK V1180L was 0.49, indicating increased sensitivity to brigatinib over non mutant EML4-ALK.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/1291
Gene URL
https://civic.genome.wustl.edu/links/genes/1
Variant URL
https://civic.genome.wustl.edu/links/variants/528
Rating
2
Evidence Type
Predictive
Disease
Lung Non-small Cell Carcinoma
Evidence Direction
Supports
Drug
Brigatinib
Evidence Level
D
Clinical Significance
Sensitivity/Response
Pubmed
25228534
Drugs
Drug NameSensitivitySupported
BrigatinibSensitivitytrue