Annotation Detail

Information
Associated Genes
NTRK3
Associated Variants
NTRK3 ETV6-NTRK3
Associated Disease
breast secretory carcinoma
Source Database
CIViC Evidence
Description
Shukla et al report on a remarkable case study of a 14 year old pediatric patient with refractory secretory breast carcinoma first presenting as a fibroadenoma at 8 yo. Over the next years, she experienced recurrence, multiple rounds of chemotherapy and metastasis -- until her case was presented at a virtual multidisciplinary tumor board organized by the Global Cancer Institute which recommended testing for ETV6-NTRK3 fusion. This fusion was confirmed by RNA-seq, targeted DNA and WGS sequencing as well as immunohistochemistry staining with a TRK antibody. The patient was treated with LOXO-101 (larotrectinib) in a single patient use protocol. Within two months, she experienced near complete resolution of a 10.4 × 8.5 cm fungating chest mass with multiple satellite lesions (See Figure 2). The authors note that TERT promoter mutation and a reciprocal inversion including CDKN2A were also identified, but given what is known about LOXO-101 and ETV6-NTRK3, they infer ETV6-NTRK3 fusion as the primary mitogenic driver in this patient.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/6475
Gene URL
https://civic.genome.wustl.edu/links/genes/3985
Variant URL
https://civic.genome.wustl.edu/links/variants/801
Rating
3
Evidence Type
Predictive
Disease
Breast Secretory Carcinoma
Evidence Direction
Supports
Drug
Larotrectinib
Evidence Level
C
Clinical Significance
Sensitivity/Response
Pubmed
29623306
Drugs
Drug NameSensitivitySupported
LarotrectinibSensitivitytrue