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Updated: Aug 18, 2025

Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells
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TRK Protein Expression in Merkel Cell Carcinoma Is Not Caused by NTRK Fusions

Rocco Cappellesso1, Lorenzo Nicolè2,3, Paolo Del Fiore4

  • 1Pathological Anatomy Unit, Padua University Hospital, 35121 Padua, Italy.

International Journal of Molecular Sciences
|December 11, 2022
PubMed

Insights

Neurotrophin receptor tyrosine kinase (NTRK) gene fusions were investigated in Merkel cell carcinoma (MCC). Despite pan-TRK expression in some MCCs, no NTRK fusions were detected, suggesting physiological TRK expression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Dermatology

Background:

  • Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer with neuroendocrine features.
  • Limited treatment options exist for advanced MCC, necessitating novel therapeutic strategies.
  • Neurotrophin receptor tyrosine kinase (NTRK) gene fusions are actionable targets in various cancers.

Purpose of the Study:

  • To investigate the presence of NTRK gene fusions in Merkel cell carcinoma.
  • To determine if TRK expression in MCC is associated with NTRK gene fusions.

Main Methods:

  • Analysis of 76 MCC samples using pan-TRK immunohistochemistry.
  • Positive cases were further analyzed by real-time RT-PCR, RNA-based NGS, and FISH to detect NTRK fusions.

Main Results:

  • 34 out of 76 MCCs exhibited pan-TRK expression.
  • No NTRK gene fusions were identified in any of the analyzed MCC cases.
  • TRK expression in MCC appears to be physiological, not driven by gene fusions.

Conclusions:

  • NTRK gene fusions are not a feature of Merkel cell carcinoma.
  • TRK expression in MCC is likely a physiological phenomenon.
  • Targeted therapy with NTRK inhibitors is unlikely to be effective in MCC.
Keywords:
EPR17341Merkel cell carcinomaNTRK1NTRK2NTRK3

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