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

Catherine M. Albert, Jessica Davis, Noah Federman, Michela Casanova, Theodore W. Laetsch

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)513-524
Number of pages12
JournalJournal of clinical oncology : official journal of the American Society of Clinical Oncology
Volume37
Issue number6
DOIs
StatePublished - Feb 20 2019

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Neoplasms
Mesoblastic Nephroma
Pediatrics
Breast Neoplasms
Genetic Translocation
Fibrosarcoma
Gene Fusion
Nerve Growth Factors
Receptor Protein-Tyrosine Kinases
Salivary Glands
Fluorescence In Situ Hybridization
Glioma
Sarcoma
Leukemia
Phosphotransferases
Immunohistochemistry

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

TRK Fusion Cancers in Children : A Clinical Review and Recommendations for Screening. / Albert, Catherine M.; Davis, Jessica; Federman, Noah; Casanova, Michela; Laetsch, Theodore W.

In: Journal of clinical oncology : official journal of the American Society of Clinical Oncology, Vol. 37, No. 6, 20.02.2019, p. 513-524.

Research output: Contribution to journalArticle

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