Annotation Detail

Information
Associated Genes
ALK
Associated Variants
ALK p.Ile1171Thr (p.I1171T) ALK p.Ile1171Thr (p.I1171T)
Associated Disease
lung non-small cell carcinoma
Source Database
CIViC Evidence
Description
Ba/F3 cells expressing EML4-ALK variant 3 with ALK I1171T mutation were treated with ceritinib, and survival IC50 of 2.6 nM was observed, which compares favorably with highly ceritinib sensitive EML4-ALK wild-type variant 1 survival IC50 of 1.7 nM reported from parallel experiments. Tumors from mice with EML4-ALK variant 3 H2228 NSCLC cell xenografts which had progressed after approximately 40 days of crizotinib treatment were sequenced for ALK mutations. I1171T was found as one of 6 ALK resistance mutations from 80 sequenced tumors. Treatment of these mouse xenograft models with ceritinib reduced tumor volume to zero, while in contrast tumor size increased with crizotinib treatment.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/1344
Gene URL
https://civic.genome.wustl.edu/links/genes/1
Variant URL
https://civic.genome.wustl.edu/links/variants/527
Rating
4
Evidence Type
Predictive
Disease
Lung Non-small Cell Carcinoma
Evidence Direction
Supports
Drug
Ceritinib
Evidence Level
D
Clinical Significance
Sensitivity/Response
Pubmed
24675041
Drugs
Drug NameSensitivitySupported
CeritinibSensitivitytrue