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Updated: Oct 20, 2025
Integration of Wet and Dry Bench Processes Optimizes Targeted Next-generation Sequencing of Low-quality and Low-quantity Tumor Biopsies
Published on: April 11, 2016
NTRK insights: best practices for pathologists
1Molecular Pathologist, Neogenomics 9490 NeoGenomics Way, Fort Myers, FL, 33912, USA. jaclyn.hechtman@neogenomics.com.
Abstract:
Since the discovery of an oncogenic tropomyosin-receptor kinase (TRK) fusion protein in the early 1980s, our understanding of neurotrophic tropomyosin-receptor kinase (NTRK) fusions, their unique patterns of frequency in different tumor types, and methods to detect them have grown in scope and depth. Identification of these molecular alterations in the management of patients with cancer has become increasingly important with the emergence of histology-agnostic, US Food and Drug Administration-approved, effective TRK protein inhibitors. Herein, we review the biology of TRK in normal and malignant tissues, as well as the prevalence and enrichment patterns of these fusions across tumor types. Testing methods currently used to identify NTRK1-3 fusions will be reviewed in detail, with attention to newer assays including RNA-based next-generation sequencing. Recently proposed algorithms for NTRK fusion testing will be compared, and practical insights provided on how testing can best be implemented and communicated within the multidisciplinary healthcare team.
Insights
Neurotrophic tropomyosin-receptor kinase (NTRK) fusions are key cancer alterations. Identifying these fusions enables targeted therapy with TRK inhibitors, improving patient outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Neurotrophic tropomyosin-receptor kinase (NTRK) fusions are oncogenic drivers discovered in the 1980s.
- Their prevalence varies across different cancer types.
- Effective TRK protein inhibitors, approved by the FDA, are now available.
Purpose of the Study:
- To review the biology of TRK in normal and malignant tissues.
- To discuss the prevalence and patterns of NTRK fusions in various tumors.
- To detail current and emerging methods for NTRK fusion detection.
Main Methods:
- Literature review of NTRK fusion biology, prevalence, and detection methods.
- Detailed examination of existing and novel diagnostic assays, including RNA-based next-generation sequencing.
- Comparison of proposed algorithms for NTRK fusion testing.
Main Results:
- NTRK fusions are important molecular targets in cancer management.
- Understanding fusion patterns aids in identifying susceptible patient populations.
- RNA-based next-generation sequencing offers advanced detection capabilities.
Conclusions:
- Accurate identification of NTRK fusions is crucial for guiding targeted therapy.
- Emerging testing strategies enhance diagnostic sensitivity and specificity.
- Effective communication of testing results within multidisciplinary teams is vital for optimal patient care.
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