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Tobias Raphael Overbeck1,2, Annika Reiffert3, Katja Schmitz3,4

  • 1Department of Hematology and Medical Oncology, University Medical Center Göttingen, 37075 Göttingen, Germany.

Cancers
|June 10, 2023
PubMed
Summary

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This summary is machine-generated.

Neurotrophic tyrosine kinase (NTRK) fusions are rare in non-small cell lung cancer (NSCLC), found in less than 1% of patients. Immunohistochemistry (IHC) followed by RNA-NGS is a feasible screening approach for NTRK fusions.

Area of Science:

  • Oncology
  • Molecular Diagnostics
  • Genetics

Background:

  • Non-small cell lung cancer (NSCLC) diagnosis relies on identifying actionable molecular alterations.
  • Neurotrophic tyrosine kinase (NTRK) fusions are rare but targetable genetic alterations in NSCLC.
  • Current diagnostic pathways for NSCLC may not optimally detect NTRK fusions.

Purpose of the Study:

  • To determine the prevalence of NTRK fusions in a routine NSCLC diagnostic setting.
  • To evaluate the feasibility of screening strategies including immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and RNA-based next-generation sequencing (RNA-NGS).

Main Methods:

  • Screened 1068 NSCLC patients using IHC followed by RNA-NGS (n=973) or direct FISH (n=95).
  • Investigated NTRK fusions and their co-occurrence with other common NSCLC driver mutations (EGFR, ALK, ROS1, BRAF, RET, KRAS).
Keywords:
FISHNSCLCNTRKRNA-based next-generation sequencingfluorescence in situ hybridizationimmunohistochemistrylung cancertargeted therapy

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Main Results:

  • NTRK fusions were identified in 0.2% of unselected NSCLC patients (2/1068).
  • Immunohistochemistry (IHC) identified 14.8% of patients as positive, with subsequent RNA-NGS confirming NTRK fusions in 30.5% of IHC-positive cases after excluding other alterations.
  • NTRK fusions were mutually exclusive with EGFR, ALK, ROS1, BRAF, RET, and KRAS alterations.

Conclusions:

  • NTRK fusion-positive NSCLC is rare, representing less than 1% of all NSCLC cases.
  • RNA-NGS and FISH are reliable methods for detecting NTRK fusions in clinical practice.
  • A diagnostic workflow incorporating pan-Trk IHC followed by RNA-NGS is recommended, potentially excluding patients with concurrent common mutations to refine detection.