Annotation Detail

Information
Associated Genes
ALK
Associated Variants
ALK CLTC-ALK
Associated Disease
diffuse large B-cell lymphoma
Source Database
CIViC Evidence
Description
A cell line called LM1 was established from the bone marrow of a 13 year old female patient with relapsed CLTC-ALK positive diffuse large B-cell lymphoma (DLBCL). The patient had been heavily treated with chemotherapy before establishment of the cell line. The cell line maintained the tumor immunophenotype. SNP analysis of patient bone marrow mononuclear cells and LM1 showed chromosomal changes associated with the cell line but 94.7% of SNPs were identically called. ALK kinase inhibitor TAE684 induced cell death in LM1 cells at low nanomolar concentrations, while it did not significantly effect the ALK-rearrangement negative DLBCL cell line Karpas422. LM1 cells formed tumors in 3/10 SCID and 9/10 NOD-SCID mice. CD30 and CD138 immmunostaining were maintained between original tumor and LM1 xenografts. In mice, LM1 but not Karpas422 xenografts regressed with TAE684 administration, and complete remission for 13 weeks was observed before experiment was terminated.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/1261
Gene URL
https://civic.genome.wustl.edu/links/genes/1
Variant URL
https://civic.genome.wustl.edu/links/variants/520
Rating
4
Evidence Type
Predictive
Disease
Diffuse Large B-cell Lymphoma
Evidence Direction
Supports
Drug
TAE684
Evidence Level
D
Clinical Significance
Sensitivity/Response
Pubmed
21494621
Drugs
Drug NameSensitivitySupported
TAE684Sensitivitytrue