Annotation Detail

Information
Associated Genes
ALK
Associated Variants
ALK p.Phe1245Cys (p.F1245C) ALK p.Phe1245Cys (p.F1245C)
Associated Disease
lung non-small cell carcinoma
Source Database
CIViC Evidence
Description
A 52 year old male never smoker was diagnosed with stage IV NSCLC adenocarcinoma and was treated with chemotherapy with eventual disease progression. He tested positive for ALK rearrangement via break apart FISH assay, and started crizotinib with near complete response for 27 months. Progression then occurred and biopsy of a pleural nodule was performed with hybrid-capture NGS. EML4-ALK variant 3 with F1245C mutation was found with allele frequency of 2% and tumor purity 13%. Due to slow progression and low tumor burden crizotinib was maintained for additional 8 months, and then he was transitioned onto ceritinib at 750 mg daily. After 3 months ceritinib, complete radiographic response was seen and the patient was without evidence of disease at 6 months. Dose was reduced to 600 mg ceritinib daily due to gastrointestinal side effects.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/1338
Gene URL
https://civic.genome.wustl.edu/links/genes/1
Variant URL
https://civic.genome.wustl.edu/links/variants/551
Rating
3
Evidence Type
Predictive
Disease
Lung Non-small Cell Carcinoma
Evidence Direction
Supports
Drug
Ceritinib
Evidence Level
C
Clinical Significance
Sensitivity/Response
Pubmed
26775591
Drugs
Drug NameSensitivitySupported
CeritinibSensitivitytrue