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
A cohort of pediatric neuroblastoma patients ages 12 months to 22 years were assessed for response to crizotinib in a Phase I study. 11 patients in this cohort had characterized ALK mutations, 4 of which were R1275Q mutation. Two of these R1275Q mutations were germline and two were somatic. Of these 2 somatic R1275Q patients, 1 showed progressive disease (PD) and 1 showed stable disease (SD). In contrast, of the 7 characterized patients with ALK mutations that were not R1275Q, 6 showed PD and 1 SD. The stable disease patient had an R1275L mutation in ALK. In general, patients with germline or somatic R1275Q mutations or R1275L mutations had 1 complete response, 3 SD and one PD, while patients with other ALK mutations had 6 PD.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/1270
Gene URL
https://civic.genome.wustl.edu/links/genes/1
Variant URL
https://civic.genome.wustl.edu/links/variants/9
Rating
2
Evidence Type
Predictive
Disease
Neuroblastoma
Evidence Direction
Supports
Drug
Crizotinib
Evidence Level
C
Clinical Significance
Sensitivity/Response
Pubmed
23598171
Drugs
Drug NameSensitivitySupported
CrizotinibSensitivitytrue