Annotation Detail

Information
Associated Genes
ALK
Associated Variants
ALK p.Arg1275Gln (p.R1275Q) ( ENST00000389048.8, ENST00000618119.4, ENST00000642122.1 )
ALK p.Arg1275Gln (p.R1275Q) ( ENST00000389048.8, ENST00000618119.4, ENST00000642122.1 )
Associated Disease
neuroblastoma
Source Database
CIViC Evidence
Description
In NB-1643 and LAN-5 neuroblastoma cell lines containing R1275Q mutation, PF-06463922 showed 51 and 19 fold greater effect on cell viability over crizotinib treatment respectively. ALK wild-type neuroblastoma cell lines did not show differential sensitivity to the treatments within the sensitivity range of R1275Q cells, and had IC50 values above 3800 nM to the inhibitors. NB-1653 cells induced tumors in CB17 SCID mice and crizotinib treatment inhibited tumor growth over vehicle treatment, but PF-06463922 induced complete tumor regression.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/1331
Gene URL
https://civic.genome.wustl.edu/links/genes/1
Variant URL
https://civic.genome.wustl.edu/links/variants/9
Rating
4
Evidence Type
Predictive
Disease
Neuroblastoma
Evidence Direction
Supports
Drug
Lorlatinib
Evidence Level
D
Clinical Significance
Sensitivity/Response
Pubmed
26554404
Drugs
Drug NameSensitivitySupported
LorlatinibSensitivitytrue