Annotation Detail

Information
Associated Genes
ALK
Associated Variants
ALK p.Gly1202Arg (p.G1202R) ALK p.Gly1202Arg (p.G1202R)
Associated Disease
cancer
Source Database
CIViC Evidence
Description
Ba/F3 cell line expressing EML4-ALK variant 3 with G1202R ALK mutation was assessed for alectinib sensitivity and IC50 for survival of 868 nM was reported, which was 64.4x higher than the IC50 reported for alectinib on Ba/F3 with EML4-ALK wild-type. Similar experiments using NPM-ALK instead of EML4-ALK yielded survival IC50 of 549 nM of NPM-ALK G1202R to alectinib, which was 27.9 times higher than IC50 for NPM-ALK wild-type. Western blots of Ba/F3 with NPM-ALK wild-type showed ablation of pALK levels above 100 nM alectinib, while pALK levels were essentially unchanged up to 1000 nM in NPM-ALK G1202R Ba/F3 cells.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/1350
Gene URL
https://civic.genome.wustl.edu/links/genes/1
Variant URL
https://civic.genome.wustl.edu/links/variants/171
Rating
3
Evidence Type
Predictive
Disease
Cancer
Evidence Direction
Supports
Drug
Alectinib
Evidence Level
D
Clinical Significance
Resistance
Pubmed
25727400
Drugs
Drug NameSensitivitySupported
AlectinibResitance or Non-Reponsetrue