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
The I1171T ALK kinase domain mutaion was found in the MGH056-1 cell line which was derived from an ALK rearranged NSCLC patient who had progressed on crizotinib and then on alectinib given at lower dose (300mg twice daily). Ectopic expression of EML4-ALK I1171T in Ba/F3 cells made these cells moderately resistant to crizotinib and resistant to alectinib. In contrast, the frequently used tool compound TAE684 was equally effective against EML4-ALK wild-type and I1171T, causing cell death at 1000x lower concentration then in unaltered Ba/F3 cells supplemented with IL3.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/1285
Gene URL
https://civic.genome.wustl.edu/links/genes/1
Variant URL
https://civic.genome.wustl.edu/links/variants/527
Rating
3
Evidence Type
Predictive
Disease
Lung Non-small Cell Carcinoma
Evidence Direction
Supports
Drug
TAE684
Evidence Level
D
Clinical Significance
Sensitivity/Response
Pubmed
25228534
Drugs
Drug NameSensitivitySupported
TAE684Sensitivitytrue