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NTRK-fusions in pediatric thyroid tumors: Current state and future perspectives

  • Author Footnotes
    # Contributed equally to this work.
    Victoria Casado-Medrano
    Footnotes
    # Contributed equally to this work.
    Affiliations
    Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia, 816-C, Philadelphia, PA 19104, United States
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  • Author Footnotes
    # Contributed equally to this work.
    Alison O'Neill
    Footnotes
    # Contributed equally to this work.
    Affiliations
    Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia, 816-C, Philadelphia, PA 19104, United States
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  • Stephen Halada
    Affiliations
    Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia, 816-C, Philadelphia, PA 19104, United States
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  • Theodore W. Laetsch
    Affiliations
    Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA, United States

    Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
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  • Andrew J. Bauer
    Affiliations
    Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia, 816-C, Philadelphia, PA 19104, United States
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  • Aime T. Franco
    Correspondence
    Corresponding author.
    Affiliations
    Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia, 816-C, Philadelphia, PA 19104, United States

    Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
    Search for articles by this author
  • Author Footnotes
    # Contributed equally to this work.

      Highlights

      • Somatic NTRK1 and NTRK3 fusions have high specificity for papillary thyroid cancer.
      • In pediatric PTC, NTRK fusions are associated with a high rate of regional and distant metastases.
      • Future studies needed to develop clinically relevant pediatric models of thyroid cancer.

      Abstract

      Pediatric and adult papillary thyroid cancer (PTC) share many similar oncogenic drivers, but differ in the pathological features and outcomes of the disease. The most frequent genetic alterations in adult PTCs are mutually exclusive point mutations in BRAF or the RAS family. In pediatric PTC, fusion oncogenes involving chromosomal translocations in tyrosine kinase (TK) receptors, most commonly RET and NTRK, are the most common genetic alterations observed. This review of the literature describes the current state of translational research in pediatric NTRK-driven thyroid cancer and highlights opportunities to improve our understanding and current models of pediatric PTC.

      Keywords

      Abbreviations:

      PTC (Papillary thyroid cancer), NIS (Sodium-iodide symporter), RAI (Radioactive iodine)
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