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Updated: Jun 26, 2025
Oncogenic Gene Fusion Detection Using Anchored Multiplex Polymerase Chain Reaction Followed by Next Generation Sequencing
Published on: July 5, 2019
NTRK gene fusion testing and management in lung cancer
Matteo Repetto1, Marina Chiara Garassino2, Herbert H Loong3
1Memorial Sloan Kettering Cancer Center, New York, NY, USA; Weill Cornell Medical College, New York, NY, USA.
Abstract:
Neurotrophic tyrosine receptor kinase (NTRK) gene fusions are recurrent oncogenic drivers found in a variety of solid tumours, including lung cancer. Several tropomyosin receptor kinase (TRK) inhibitors have been developed to treat tumours with NTRK gene fusions. Larotrectinib and entrectinib are first-generation TRK inhibitors that have demonstrated efficacy in patients with TRK fusion lung cancers. Genomic testing is recommended for all patients with metastatic non-small cell lung cancer for optimal drug therapy selection. Multiple testing methods can be employed to identify NTRK gene fusions in the clinic and each has its own advantages and limitations. Among these assays, RNA-based next-generation sequencing (NGS) can be considered a gold standard for detecting NTRK gene fusions; however, several alternatives with minimally acceptable sensitivity and specificity are also available in areas where widespread access to NGS is unfeasible. This review highlights the importance of testing for NTRK gene fusions in lung cancer, ideally using the gold-standard method of RNA-based NGS, the various assays that are available, and treatment algorithms for patients.
Insights
Testing for neurotrophic tyrosine receptor kinase (NTRK) gene fusions is crucial for lung cancer patients. RNA-based next-generation sequencing (NGS) is the gold standard for identifying these fusions, guiding targeted therapy selection.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Neurotrophic tyrosine receptor kinase (NTRK) gene fusions are key drivers in various solid tumors, including lung cancer.
- Tropomyosin receptor kinase (TRK) inhibitors like larotrectinib and entrectinib show efficacy in treating NTRK fusion-positive lung cancers.
Purpose of the Study:
- To emphasize the significance of NTRK gene fusion testing in lung cancer management.
- To review available diagnostic assays and treatment strategies for NTRK fusion-positive lung cancer.
Main Methods:
- Discussion of RNA-based next-generation sequencing (NGS) as the gold standard for NTRK fusion detection.
- Exploration of alternative diagnostic methods with varying sensitivity and specificity.
- Review of current treatment algorithms for patients with NTRK gene fusions.
Main Results:
- Genomic testing, particularly for NTRK gene fusions, is vital for optimal drug selection in metastatic non-small cell lung cancer.
- RNA-based NGS offers superior accuracy for NTRK fusion identification.
- Alternative assays are available but may have limitations in sensitivity and specificity.
Conclusions:
- Accurate detection of NTRK gene fusions is essential for personalized lung cancer therapy.
- RNA-based NGS is the preferred method for identifying NTRK fusions.
- Understanding available testing modalities and treatment options improves patient outcomes.
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