Annotation Detail

Information
Associated Genes
ALK
Associated Variants
ALK EML4-ALK C1156Y–L1198F
Associated Disease
lung non-small cell carcinoma
Source Database
CIViC Evidence
Description
Case report of a patient with metastatic ALK-rearranged NSCLC. After developing resistance to first and second line ALK inhibitors mediated by a C1156Y mutation, the patient had a partial response with the third generation ALK-inhibitor lorlatinib. The patient progressed on lorlatinib after 8 months, at which point whole exome sequencing revealed an EML4-ALK C1156Y–L1198F double mutation. In vitro, the double mutation was resistant to lorlatinib but sensitive to crizotinib. The patient was started on crizotinib again and had a clinical response that lasted for 6 months.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/844
Gene URL
https://civic.genome.wustl.edu/links/genes/1
Variant URL
https://civic.genome.wustl.edu/links/variants/352
Rating
4
Evidence Type
Predictive
Disease
Lung Non-small Cell Carcinoma
Evidence Direction
Supports
Drug
Crizotinib
Evidence Level
C
Clinical Significance
Sensitivity/Response
Pubmed
26698910
Drugs
Drug NameSensitivitySupported
CrizotinibSensitivitytrue