Annotation Detail

Information
Associated Genes
ALK
Associated Variants
ALK p.Phe1174Leu (p.F1174L) ( ENST00000389048.8, ENST00000618119.4, ENST00000642122.1 )
ALK p.Phe1174Leu (p.F1174L) ( ENST00000618119.4, ENST00000642122.1, ENST00000389048.8 )
Associated Disease
neuroblastoma
Source Database
CIViC Evidence
Description
The SH-SY5Y neuroblastoma cell line containing the F1174L ALK mutation was found to undergo cell death when treated with the ALK/IGF1R inhibitor AZD3463. These cells were more sensitive than other neuroblastoma cell lines containing wild-type ALK. Marked inhibition of soft agar colony formation of SH-SY5Y cells was also observed with drug treatment. AZD3463 inhibited Akt signaling in these cells within two hours of treatment, and activated apoptosis and autophagy pathways. Treatment of SH-SY5Y cells implanted into left kidneys of nude mice resulted in almost complete tumor regression.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/1327
Gene URL
https://civic.genome.wustl.edu/links/genes/1
Variant URL
https://civic.genome.wustl.edu/links/variants/8
Rating
3
Evidence Type
Predictive
Disease
Neuroblastoma
Evidence Direction
Supports
Drug
AZD3463
Evidence Level
D
Clinical Significance
Sensitivity/Response
Pubmed
26786851
Drugs
Drug NameSensitivitySupported
AZD3463Sensitivitytrue