TRK Fusion Cancers in Children: A Clinical Review and Recommendations for Screening

J Clin Oncol. 2019 Feb 20;37(6):513-524. doi: 10.1200/JCO.18.00573. Epub 2018 Dec 28.


Chromosomal translocations involving the NTRK1, NTRK2, and NTRK3 genes (TRK fusions), which encode the neurotrophin tyrosine kinase receptors TRKA, TRKB, and TRKC, can result in constitutive activation and aberrant expression of TRK kinase. Certain cancers almost universally harbor TRK fusions, including infantile fibrosarcoma, cellular congenital mesoblastic nephroma, secretory breast cancer, and mammary analog secretory carcinoma of the salivary gland. TRK fusions have also been identified at lower frequencies across a broad range of other pediatric cancers, including undifferentiated sarcomas, gliomas, papillary thyroid cancers, spitzoid neoplasms, inflammatory myofibroblastic tumors, and acute leukemias. Here we review the prevalence and diseases associated with TRK fusions and methods of detection of these fusions in light of the recent development of selective TRK inhibitors, such as larotrectinib, which demonstrated a 75% response rate across children and adults with TRK fusion cancers. We provide recommendations for screening pediatric tumors for the presence of TRK fusions, including the use of immunohistochemistry or fluorescence in situ hybridization for patients with tumors likely to harbor TRK fusions. Further, we recommend next-generation sequencing for tumors that have a relatively low prevalence of TRK fusions, both to identify patients who may benefit from TRK inhibition and to identify other targetable oncogenic drivers that exist in the same tumor types.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Age of Onset
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / antagonists & inhibitors
  • Biomarkers, Tumor / genetics*
  • Gene Fusion*
  • Genetic Predisposition to Disease
  • Genetic Testing / standards*
  • High-Throughput Nucleotide Sequencing / standards
  • Humans
  • Immunohistochemistry / standards
  • In Situ Hybridization, Fluorescence / standards
  • Membrane Glycoproteins / antagonists & inhibitors
  • Membrane Glycoproteins / genetics*
  • Neoplasms / drug therapy
  • Neoplasms / genetics*
  • Neoplasms / mortality
  • Neoplasms / pathology
  • Phenotype
  • Practice Guidelines as Topic / standards*
  • Predictive Value of Tests
  • Protein Kinase Inhibitors / therapeutic use
  • Receptor, trkA / antagonists & inhibitors
  • Receptor, trkA / genetics*
  • Receptor, trkB / antagonists & inhibitors
  • Receptor, trkB / genetics*
  • Receptor, trkC / antagonists & inhibitors
  • Receptor, trkC / genetics*


  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Membrane Glycoproteins
  • NTRK1 protein, human
  • Protein Kinase Inhibitors
  • Receptor, trkA
  • Receptor, trkB
  • Receptor, trkC
  • tropomyosin-related kinase-B, human