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Updated: Jul 16, 2025
Oncogenic Gene Fusion Detection Using Anchored Multiplex Polymerase Chain Reaction Followed by Next Generation Sequencing
Published on: July 5, 2019
Brazilian Expert Consensus for NTRK Gene Fusion Testing in Solid Tumors
Mariana Petaccia de Macedo1,2, Ellen Caroline Toledo Nascimento3,4, Fernando Augusto Soares1,2
1Rede D'Or São Luiz, São Paulo, Brazil.
Abstract:
Oncogenic neurotrophic tropomyosin receptor kinase gene fusions occur in less than 1% of common cancers. These mutations have emerged as new biomarkers in cancer genomic profiling with the approval of selective drugs against tropomyosin receptor kinase fusion proteins. Nevertheless, the optimal pathways and diagnostic platforms for this biomarker's screening and genomic profiling have not been defined and remain a subject of debate. A panel of national experts in molecular cancer diagnosis and treatment was convened by videoconference and suggested topics to be addressed in the literature review. The authors proposed a testing algorithm for oncogenic neurotrophic tropomyosin receptor kinase gene fusion screening and diagnosis for the Brazilian health system. This review aims to discuss the latest literature evidence and international consensus on neurotrophic tropomyosin receptor kinase gene fusion diagnosis to devise clinical guidelines for testing this biomarker. We propose an algorithm in which testing for this biomarker should be requested to diagnose advanced metastatic tumors without known driver mutations. In this strategy, Immunohistochemistry should be used as a screening test followed by confirmatory next-generation sequencing in immunohistochemistry-positive cases.
Insights
Neurotrophic tropomyosin receptor kinase (NTRK) gene fusions are rare cancer biomarkers. This review proposes an algorithm using immunohistochemistry screening followed by next-generation sequencing confirmation for NTRK fusion diagnosis.
Area of Science:
- Oncology
- Molecular Diagnostics
- Genomics
Background:
- Oncogenic neurotrophic tropomyosin receptor kinase (NTRK) gene fusions are rare but actionable biomarkers in various cancers.
- The emergence of targeted therapies necessitates clear diagnostic strategies for NTRK fusions.
- Current optimal screening and diagnostic platforms for NTRK fusions remain debated.
Purpose of the Study:
- To review the latest evidence and international consensus on NTRK gene fusion diagnosis.
- To propose a clinical guideline and testing algorithm for NTRK fusion biomarker diagnosis.
- To adapt diagnostic strategies for the Brazilian healthcare system.
Main Methods:
- Literature review of current evidence and international guidelines on NTRK fusion diagnosis.
- Convening a panel of national experts in molecular cancer diagnosis and treatment.
- Development of a proposed testing algorithm for NTRK gene fusion screening.
Main Results:
- NTRK gene fusions are identified in less than 1% of common cancers.
- Immunohistochemistry (IHC) is proposed as an effective screening method.
- Next-generation sequencing (NGS) is recommended for confirmatory testing in IHC-positive cases.
Conclusions:
- An integrated diagnostic approach utilizing IHC and NGS is recommended for NTRK fusions.
- Testing for NTRK fusions should be considered in advanced metastatic tumors lacking known driver mutations.
- The proposed algorithm aims to standardize NTRK fusion diagnosis within the Brazilian health system.
