Annotation Detail

Information
Associated Genes
ALK
Associated Variants
ALK DEL4-11
ALK DEL4-11
Associated Disease
neuroblastoma
Source Database
CIViC Evidence
Description
The MYCN amplification positive relapsed neuroblastoma-derived cell line CLB-BAR contains the driver ALK DEL 11-14 mutation, which removes extracellular domain exons 4 through 11. Brigatinib treatment of CLB-BAR cells reduced MYCN protein levels and ALK phosphorylation (Y1604) similar to crizotnib. Brigatinib reduced CLB-BAR cellular proliferation more effectively than crizotinib (IC50 75.2 vs 186.4nM). CLB-BAR xenografts in BalbC/NUDE mice responded to brigatinib with reduced tumor volume and weight (N=8/group) as well as reduced ALK phosphorylation and MYCN levels compared to untreated controls. Release of brigatinib administration at day 15 resulted in tumor growth (N=2).
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/1336
Gene URL
https://civic.genome.wustl.edu/links/genes/1
Variant URL
https://civic.genome.wustl.edu/links/variants/550
Rating
3
Evidence Type
Predictive
Disease
Neuroblastoma
Evidence Direction
Supports
Drug
Brigatinib
Evidence Level
D
Clinical Significance
Sensitivity/Response
Pubmed
27049722
Drugs
Drug NameSensitivitySupported
BrigatinibSensitivitytrue