Recurrent SPECC1L-NTRK fusions in pediatric sarcoma and brain tumors

Cold Spring Harb Mol Case Stud. 2020 Dec 17;6(6):a005710. doi: 10.1101/mcs.a005710. Print 2020 Dec.


The identification of rearrangements driving expression of neurotrophic receptor tyrosine kinase (NTRK) family kinases in tumors has become critically important because of the availability of effective, specific inhibitor drugs. Whole-genome sequencing (WGS) combined with RNA sequencing (RNA-seq) can identify novel and recurrent expressed fusions. Here we describe three SPECC1L-NTRK fusions identified in two pediatric central nervous system cancers and an extracranial solid tumor using WGS and RNA-seq. These fusions arose either through a simple balanced rearrangement or in the context of a complex chromoplexy event. We cloned the SPECC1L-NTRK2 fusion directly from a patient sample and showed that enforced expression of this fusion is sufficient to promote cytokine-independent survival and proliferation. Cells transformed by SPECC1L-NTRK2 expression are sensitive to a TRK inhibitor drug. We report here that SPECC1L-NTRK fusions can arise in a range of pediatric cancers. Although WGS and RNA-seq are not required to detect NTRK fusions, these techniques may be of benefit when NTRK fusions are not suspected on clinical grounds or not identified by other methods.

Keywords: neoplasm of the central nervous system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / pathology
  • Central Nervous System Neoplasms / genetics
  • Child
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Infant
  • Male
  • Membrane Glycoproteins / genetics*
  • Oncogene Proteins, Fusion / genetics*
  • Phosphoproteins / genetics*
  • Protein Kinase Inhibitors
  • Receptor, trkA / genetics*
  • Receptor, trkB / genetics*
  • Sarcoma / genetics*
  • Sarcoma / pathology
  • Whole Genome Sequencing


  • Biomarkers, Tumor
  • Membrane Glycoproteins
  • NTRK1 protein, human
  • Oncogene Proteins, Fusion
  • Phosphoproteins
  • Protein Kinase Inhibitors
  • SPECC1L protein, human
  • Receptor, trkA
  • Receptor, trkB
  • tropomyosin-related kinase-B, human