Annotation Detail
Information
- Associated Genes
- NTRK1
- Associated Variants
- NTRK1 LMNA-NTRK1 G595R AND G667C
- Associated Disease
- colorectal adenocarcinoma
- Source Database
- CIViC Evidence
- Description
- A gene fusion between exon 10 of NTRK1 and exon 11 of the LMNA genes was observed in a patient with metastatic colorectal cancer after therapy with first-line FOLFOX, second-line FOLFIRI/cetuximab, and third-line irinotecan. The patient treated in a clinical trial with pan-TRK kinase inhibitor entrectinib. Treatment was well tolerated and led to a partial response (PR) with 30% tumor shrinkage of multiple liver metastases. Clinical response lasted 4 months. Longitudinal analysis of ctDNA in plasma samples revealed a p.G595R- and p.G667C mutation in NTRK1 that were absent before treatment initiation but emerged 4 weeks upon initiation of treatment with entrectinib. These mutations were also validated using xenograft, in vitro and 3D-modeling.
- Variant Origin
- somatic
- Variant Origin
- Somatic
- Evidence URL
- https://civic.genome.wustl.edu/links/evidence_items/2961
- Gene URL
- https://civic.genome.wustl.edu/links/genes/3983
- Variant URL
- https://civic.genome.wustl.edu/links/variants/1282
- Rating
- 4
- Evidence Type
- Predictive
- Disease
- Colorectal Adenocarcinoma
- Evidence Direction
- Supports
- Drug
- Entrectinib
- Evidence Level
- C
- Clinical Significance
- Resistance
- Pubmed
- 26546295
Drugs
| Drug Name | Sensitivity | Supported |
|---|---|---|
| Entrectinib | Resitance or Non-Reponse | true |