Annotation Detail

Information
Associated Genes
ALK
Associated Variants
ALK ALTERNATIVE TRANSCRIPT (ATI)
ALK ALTERNATIVE TRANSCRIPT (ATI)
Associated Disease
mucosal melanoma
Source Database
CIViC Evidence
Description
ALK expression was analyzed in 45 melanoma patient-derived xenografts (PDXs), with 11/45 showing ALK expression. Four PDX tumours had only wild-type ALK expression, four had only ALK alternative transcript (ATI) expression, two had wild-type and ATI expression, and one had ALK ATI and multiple EML4-ALK fusion variants. In vitro and in vivo experiments showed that an EML4-ALK fusion expressing sample responded to ALK inhibitors while wild-type ALK and ALK ATI expressing samples did not. Decreased activity in downstream signaling targets with ALK inhibitor treatment was noted for samples expressing fusion ALK but not those expressing only ALK ATI. Further, a patient with metastatic mucosal melanoma expressing ALK ATI was treated with the ALK/ROS1/TRK inhibitor entrectinib but experienced rapid clinical and radiologic progression resulting in treatment discontinuation after two weeks.
Variant Origin
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/7421
Gene URL
https://civic.genome.wustl.edu/links/genes/1
Variant URL
https://civic.genome.wustl.edu/links/variants/839
Rating
4
Evidence Type
Predictive
Disease
Mucosal Melanoma
Evidence Direction
Does Not Support
Drug
Entrectinib
Evidence Level
C
Clinical Significance
Sensitivity/Response
Pubmed
29054983
Drugs
Drug NameSensitivitySupported
EntrectinibSensitivityfalse