Annotation Detail

Information
Associated Genes
ALK
Associated Variants
ALK EML4-ALK T1151INST
Associated Disease
lung non-small cell carcinoma
Source Database
CIViC Evidence
Description
Ba/F3 cells transduced with EML4-ALK 1151 insT were treated with 17-AAG producing an IC50 value of 44.5 nM, which was 0.4 times that reported for EML4-ALK wildtype in Ba/F3, indicating possible increased dependence of EML4-ALK 1151 insT on HSP90. 17-AAG also reduced survival of the parental IL3-dependent Ba/F3 cells (183.7 nM), indicating increased nonspecific effects of 17_AAG treatment. Crizotinib resistant clones were produced from the parental EML4-ALK variant 1 containing cell line H3122 (CR1, CR2, CR3). H3122 CR2 was found to contain the EML4-ALK InsT variant. H3122 CR2 and H3122 cells were similarly sensitized to 17-AAG death with an IC50 value of approximately 5 nM, while control cells without EML4-ALK had IC50 values approximately 10x higher.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/1349
Gene URL
https://civic.genome.wustl.edu/links/genes/1
Variant URL
https://civic.genome.wustl.edu/links/variants/173
Rating
2
Evidence Type
Predictive
Disease
Lung Non-small Cell Carcinoma
Evidence Direction
Supports
Drug
Tanespimycin
Evidence Level
D
Clinical Significance
Sensitivity/Response
Pubmed
22277784
Drugs
Drug NameSensitivitySupported
TanespimycinSensitivitytrue