Related Experiment Video
Updated: Jul 26, 2025
Oncogenic Gene Fusion Detection Using Anchored Multiplex Polymerase Chain Reaction Followed by Next Generation Sequencing
Published on: July 5, 2019
NTRK fusions in solid tumours: what every pathologist needs to know
Minh Anh Nguyen1, Andrew J Colebatch2, Diana Van Beek1
1Department of Tissue Pathology and Diagnostic Oncology, NSW Health Pathology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.
Abstract:
Fusions involving the Neurotrophic tropomyosin receptor kinase (NTRK) gene family (NTRK1, NTRK2 and NTRK3) are targetable oncogenic alterations that are found in a diverse range of tumours. There is an increasing demand to identify tumours which harbour these fusions to enable treatment with selective tyrosine kinase inhibitors such as larotrectinib and entrectinib. NTRK fusions occur in a wide range of tumours including rare tumours such as infantile fibrosarcoma and secretory carcinomas of the salivary gland and breast, as well as at low frequencies in more common tumours including melanoma, colorectal, thyroid and lung carcinomas. Identifying NTRK fusions is a challenging task given the different genetic mechanisms underlying NTRK fusions, their varying frequency across different tumour types, complicated by other factors such as tissue availability, optimal detection methods, accessibility and costs of testing methods. Pathologists play a key role in navigating through these complexities by determining optimal approaches to NTRK testing which has important therapeutic and prognostic implications. This review provides an overview of tumours harbouring NTRK fusions, the importance of identifying these fusions, available testing methods including advantages and limitations, and generalised and tumour-specific approaches to testing.
Insights
Identifying Neurotrophic tropomyosin receptor kinase (NTRK) gene fusions is crucial for targeted cancer therapy. This review details tumours with NTRK fusions, testing methods, and diagnostic strategies for effective treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Neurotrophic tropomyosin receptor kinase (NTRK) gene fusions (NTRK1, NTRK2, NTRK3) represent targetable oncogenic alterations across diverse tumor types.
- Identifying these fusions is critical for guiding treatment with selective tyrosine kinase inhibitors like larotrectinib and entrectinib.
- NTRK fusions are found in rare tumors (e.g., infantile fibrosarcoma) and common cancers (e.g., lung, colorectal, melanoma) at varying frequencies.
Purpose of the Study:
- To provide a comprehensive overview of tumors harboring NTRK fusions.
- To highlight the therapeutic and prognostic significance of identifying NTRK fusions.
- To discuss the challenges and optimal approaches for NTRK fusion testing in clinical practice.
Main Methods:
- Review of existing literature on NTRK fusions and associated tumors.
- Analysis of various diagnostic methods for detecting NTRK fusions, including their advantages and limitations.
- Discussion of generalized and tumor-specific testing strategies.
Main Results:
- NTRK fusions are oncogenic drivers present in a wide spectrum of malignancies.
- Accurate identification of NTRK fusions is essential for patient selection for targeted therapies.
- Pathologists play a pivotal role in selecting appropriate testing methodologies.
Conclusions:
- NTRK fusion testing is a critical component of precision oncology.
- Understanding the landscape of NTRK fusion-positive tumors and testing modalities is vital for oncologists and pathologists.
- Optimized testing strategies are necessary to ensure timely and accurate diagnosis for effective patient management.
