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Related Concept Videos

Enzyme-linked Receptors01:00

Enzyme-linked Receptors

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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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Neurotrophic receptor tyrosine kinase (NTRK) fusion testing is crucial for cancer care. This review compares NTRK testing methods, including next-generation sequencing (NGS) and immunohistochemistry, to guide pathologists in selecting optimal approaches for NTRK fusion detection.

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Area of Science:

  • Oncology
  • Molecular Diagnostics
  • Genetics

Background:

  • Neurotrophic receptor tyrosine kinase (NTRK) fusions have significant diagnostic and therapeutic implications.
  • The availability of two FDA-approved TRK inhibitors has increased the importance of NTRK fusion testing for treatment decisions.
  • The landscape of NTRK fusion testing is complex, requiring careful consideration of clinicopathologic factors.

Purpose of the Study:

  • To compare various NTRK testing methodologies.
  • To assist pathologists in understanding the features and performance of different tests.
  • To guide the selection of appropriate NTRK fusion detection methods for laboratories and patient specimens.

Main Methods:

  • A comprehensive literature search was conducted on NTRK gene fusions and TRK protein.
  • The search included studies on treatment, testing methodologies, and the prevalence of fusion-positive cases.
  • Analysis focused on comparing the characteristics and performance of different detection techniques.

Main Results:

  • Next-generation sequencing (NGS) panel testing is a cost-effective and reliable method for broad NTRK fusion detection, with performance varying by panel design and sample type (DNA/RNA).
  • Pan-TRK immunohistochemistry serves as a rapid, economical screening tool for cases not undergoing routine NGS or with unsuitable specimens.
  • Fluorescence in situ hybridization (FISH) is suitable for low-tumor-content specimens unsuitable for NGS, while quantitative reverse transcription polymerase chain reaction (qRT-PCR) is best for monitoring specific, low-level disease.

Conclusions:

  • Optimal NTRK fusion testing depends on the specific clinical scenario and laboratory capabilities.
  • Laboratories should develop tailored NTRK testing algorithms based on practice setting and patient needs.
  • Understanding the nuances of each testing method (NGS, IHC, FISH, qRT-PCR) is essential for accurate and efficient NTRK fusion detection.