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Updated: Dec 25, 2025
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 review details methods for detecting these NTRK fusions in rare and common cancers.
Area of Science:
- Oncology
- Molecular Diagnostics
- Genetics
Background:
- Tropomyosin receptor kinase (TRK) inhibitors, including FDA-approved larotrectinib, offer effective treatment for cancers with neurotrophic TRK (NTRK) gene fusions.
- NTRK fusions involve NTRK1, NTRK2, or NTRK3 genes and are key drivers in specific rare cancers and occasionally found in common malignancies.
Purpose of the Study:
- To review current methods for identifying NTRK fusions in cancer patients.
- To discuss the advantages and disadvantages of various diagnostic techniques.
- To propose an efficient strategy for detecting NTRK fusions in clinical settings.
Main Methods:
- Review of diagnostic modalities for NTRK fusion detection.
- Comparison of pan-TRK immunohistochemistry, fluorescence in situ hybridization, and sequencing methods.
- Discussion of specimen triaging based on histology and molecular findings.
Main Results:
- Multiple methods exist for NTRK fusion detection, each with unique strengths and limitations.
- The choice of testing depends on laboratory resources and economic factors.
- Histology-guided molecular testing can enhance efficiency in identifying NTRK fusion-positive tumors.
Conclusions:
- Accurate and efficient identification of NTRK fusions is vital for patient selection for TRK inhibitor therapy.
- A proposed triaging strategy aims to optimize the detection of these treatable oncogenic fusions.
- Integration of histology and molecular diagnostics is recommended for efficient NTRK fusion identification.
