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Updated: Jan 3, 2026
Oncogenic Gene Fusion Detection Using Anchored Multiplex Polymerase Chain Reaction Followed by Next Generation Sequencing
Published on: July 5, 2019
Identifying patients with NTRK fusion cancer
J P Solomon1, R Benayed1, J F Hechtman1
1Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, USA.
Abstract:
Due to the efficacy of tropomyosin receptor kinase (TRK) inhibitor therapy and the recent Food and Drug Administration approval of larotrectinib, it is now clinically important to accurately and efficiently identify patients with neurotrophic TRK (NTRK) fusion-driven cancer. These oncogenic fusions occur when the kinase domain of NTRK1, NTRK2 or NTRK3 fuse with any of a number of N-terminal partners. NTRK fusions are characteristic of a few rare types of cancer, such as secretory carcinoma of the breast or salivary gland and infantile fibrosarcoma, but they are also infrequently seen in some common cancers, such as melanoma, glioma and carcinomas of the thyroid, lung and colon. There are multiple methods for identifying NTRK fusions, including pan-TRK immunohistochemistry, fluorescence in situ hybridisation and sequencing methods, and the advantages and drawbacks of each are reviewed here. While testing algorithms will obviously depend on availability of various testing modalities and economic considerations for each individual laboratory, we propose triaging specimens based on histology and other molecular findings to most efficiently identify tumours harbouring these treatable oncogenic fusions.
Insights
Identifying neurotrophic tropomyosin receptor kinase (TRK) fusion-driven cancers is crucial for effective treatment with TRK inhibitors like larotrectinib. This study reviews methods to efficiently detect these NTRK fusions in various tumors.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Tropomyosin receptor kinase (TRK) inhibitor therapy, including FDA-approved larotrectinib, shows efficacy in treating cancers with neurotrophic TRK (NTRK) fusions.
- NTRK fusions, involving NTRK1, NTRK2, or NTRK3 genes, drive oncogenesis and are found in rare cancers and some common malignancies.
Purpose of the Study:
- To review and compare methods for accurately and efficiently identifying NTRK fusions in cancer patients.
- To propose an optimized strategy for detecting NTRK fusions based on tumor histology and molecular characteristics.
Main Methods:
- Review of existing diagnostic methods for NTRK fusion detection, including pan-TRK immunohistochemistry, fluorescence in situ hybridization, and sequencing.
- Evaluation of the advantages and limitations of each diagnostic modality.
Main Results:
- Multiple methods exist for NTRK fusion identification, each with specific benefits and drawbacks.
- Histology and other molecular findings can guide specimen triaging for efficient fusion detection.
Conclusions:
- Accurate and efficient identification of NTRK fusion-driven cancers is clinically important for targeted therapy.
- A proposed triaging strategy based on histology and molecular data can optimize the detection of these treatable oncogenic fusions.
