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Related Concept Videos

Enzyme-linked Receptors01:00

Enzyme-linked Receptors

78.9K
Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
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Oncogenic Gene Fusion Detection Using Anchored Multiplex Polymerase Chain Reaction Followed by Next Generation Sequencing
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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.

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Summary

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.

Keywords:
NTRKgene fusionimmunohistochemistrymolecular testingneurotrophic tropomyosin kinasenext generation sequencingoncogenetyrosine receptor kinase

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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.