NTRK2

Overview

NTRK2 (neurotrophic receptor tyrosine kinase 2, also known as TRKB) encodes the high-affinity receptor for brain-derived neurotrophic factor (BDNF). In neuroblastoma, NTRK2/TRKB expression is a well-established marker of poor prognosis and is co-expressed with MYCN in high-risk tumors. Single-cell studies identify NTRK2 as co-defining the novel postnatal human adrenal progenitor (hC1) and the high-risk undifferentiated neuroblastoma cluster (nC3), in direct contrast to NTRK1/TRKA which marks favorable-outcome tumors.

Alterations observed in the corpus

  • NTRK2 (TRKB) is a co-defining marker for the postnatal human progenitor hC1 and the undifferentiated high-risk neuroblastoma nC3 cluster; associated with poor outcome and co-expressed with MYCN in discrete tumor regions validated by RNAscope in situ hybridization PMID:34493726.
  • NTRK2+/CLDN11+ double-positive cells were identified by RNAscope ISH in the postnatal adrenal capsule and medulla at ages 0, 4 years, and adulthood; these cells are mutually exclusive from TH+ chromaffin cells and SOX10+ SCPs; most abundant at age 0 and declining with age PMID:34493726.
  • In a MYCN-amplified high-risk tumor (K10), RNAscope showed NTRK2+ cells surrounding NTRK1+/TH+/NTRK2− differentiating cells, illustrating intratumoral NTRK1/NTRK2 mutual exclusivity PMID:34493726.
  • NTRK1 and NTRK2 are confirmed as mutually exclusive outcome biomarkers at the single-cell level; NTRK2 high/NTRK1 low identifies the high-risk undifferentiated identity PMID:34493726.
  • NTRK2 listed as an actionable fusion target within NTRK1/NTRK2/NTRK3 panel evaluated in the 194-specimen UCLA sarcoma PDTO platform; FISH-negativity for ETV6 in SARC0127 led to reclassification away from IFS (which canonically carries ETV6–NTRK3 fusion). PMID:39305899
  • Part of NTRK family (NTRK1/2/3) with 20 total mutations in 188 LUAD tumours, 7 in kinase domains; co-occurs with FGFR4 and PDGFRA mutations. PMID:18948947
  • Two novel kinase-domain-retaining fusions identified in pilocytic astrocytoma: QKI:NTRK2 and NACC2:NTRK2 (3 non-cerebellar samples); 5’ partners contribute dimerization domains predicted to confer ligand-independent activation; NTRK2 identified as a rational therapeutic target alongside FGFR1 inhibition PMID:23817572
  • NTRK1/2/3 fusions reported in ~0.2% of CCA overall, up to 3.6% of intrahepatic CCA; targetable with entrectinib and larotrectinib PMID:25526346
  • MAPK-pathway alteration enriched in PA-like LGG (52%) and LGm6-GBM (32%) subtypes in diffuse glioma PMID:26824661
  • NTRK2 fusions identified in pan-lung cancer TCGA analysis (n=1144): TRIM24-NTRK2 in adenocarcinoma and novel NTRK2-TP63 fusion in squamous cell carcinoma PMID:27158780
  • Mentioned as a rare fusion target in young lung cancer (YLC) with scarce age-stratified frequency data PMID:27346245

Cancer types (linked)

  • NBL — NTRK2 marks the high-risk undifferentiated nC3 neuroblastoma cluster and the postnatal hC1 progenitor; correlates with MYCN amplification and poor clinical outcome PMID:34493726.

Co-occurrence and mutual exclusivity

Therapeutic relevance

  • NTRK2/TRKB is a candidate therapeutic target in high-risk neuroblastoma; NTRK2 vs NTRK1 expression ratio at the single-cell level provides a transcriptional basis for the established clinical dichotomy PMID:34493726.
  • The authors speculate that postnatally arising TRKB+/CLDN11+ cholinergic progenitors could be the cell-of-origin for high-risk neuroblastoma in older children, reframing target discovery away from SCP-based models PMID:34493726.

Open questions

  • Whether CHRNA7-mediated cholinergic signaling acts upstream of NTRK2 in the hC1 progenitor is not addressed PMID:34493726.
  • Whether NTRK2 inhibition would deplete the hC1-like nC3 subpopulation and improve outcomes has not been tested in this model PMID:34493726.

Sources

This page was processed by entity-page-writer on 2026-05-15. - PMID:18948947

This page was processed by entity-page-writer on 2026-05-15. - PMID:23817572

This page was processed by entity-page-writer on 2026-05-15. - PMID:25526346

This page was processed by entity-page-writer on 2026-05-15. - PMID:26824661

This page was processed by entity-page-writer on 2026-05-15. - PMID:27158780

This page was processed by entity-page-writer on 2026-05-15. - PMID:27346245

This page was processed by entity-page-writer on 2026-05-15.