Annotation Detail

Information
Associated Genes
NTRK1
Associated Variants
NTRK1 NTRK1-DDR2
Associated Disease
melanoma
Source Database
CIViC Evidence
Description
In this study we report that nonspitzoid metastasizing melanomas of adults may also harbor NTRK fusions and that NTRK expression can be immunohistochemically detected in these tumors. Of 751 melanomas analyzed by next-generation sequencing, 4 metastatic melanomas were identified with NTRK fusions, 3 involving NTRK1 (TRIM63, DDR2, and GON4L), 1 involving NTRK2 (TRAF2). All tumors were cytologically characterized by the presence of large epithelioid melanocytes and were immunoreactive with anti-Trk antibody. The NTRK1-DDR2 fusion occurred in a 55 yo woman with a nodular melanoma. Her primary tumor was umbilical with a metastasis to the colon. NF1 truncation and RAC1 p295 were identified as co-occurring melanoma drivers in this patient. Thus, the presence of an NTRK family fusion in nonspitzoid metastasizing melanomas of adults may provide a therapeutic opportunity for NTRK inhibitors such as larotrectinib in a small subset of patients with metastatic melanoma.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/6393
Gene URL
https://civic.genome.wustl.edu/links/genes/3983
Variant URL
https://civic.genome.wustl.edu/links/variants/2394
Rating
2
Evidence Type
Predictive
Disease
Melanoma
Evidence Direction
Supports
Drug
Larotrectinib
Evidence Level
E
Clinical Significance
Sensitivity/Response
Pubmed
29683819
Drugs
Drug NameSensitivitySupported
LarotrectinibSensitivitytrue