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Pediatric NTRK-rearranged gliomas: A clinicopathological and molecular analysis of six cases

Jing Zhao1, Feng Tian1, Di Ding1

  • 1Department of Pathology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.

Pathology, Research and Practice
|February 13, 2026
PubMed
Abstract

Insights

Pediatric gliomas with neurotrophic tyrosine receptor kinase (NTRK) gene fusions show diverse pathological and molecular features. Routine NTRK testing is recommended for all pediatric gliomas to guide targeted therapies.

Area of Science:

  • Oncology
  • Genetics
  • Pediatric Medicine

Background:

  • Neurotrophic tyrosine receptor kinase (NTRK) gene fusions are oncogenic drivers in a small percentage of gliomas.
  • Targeted therapies for NTRK-rearranged tumors offer improved outcomes, increasing focus on these rare malignancies.

Purpose of the Study:

  • To characterize the pathological and molecular diversity of pediatric NTRK-rearranged gliomas.
  • To inform the development of targeted therapeutic strategies for these tumors.

Main Methods:

  • Analysis of six pediatric gliomas with NTRK fusions using next-generation DNA sequencing and fluorescence in situ hybridization.
  • Histopathological evaluation and DNA methylation profiling.

Main Results:

  • All analyzed tumors were supratentorial, with varying histological grades and NTRK gene involvement (NTRK1, NTRK2, NTRK3).
  • Complex dual and triple gene fusions were identified, alongside additional genetic alterations in some cases.
  • DNA methylation profiling did not reveal distinct methylation classes.

Conclusions:

  • This study expands the known clinicopathological and molecular spectrum of pediatric NTRK-rearranged gliomas.
  • Complex fusion patterns and rare entities were observed.
  • Routine NTRK testing in pediatric gliomas, regardless of grade, is supported to facilitate targeted treatment.
Keywords:
DNA methylation profileGliomaInfant-type hemispheric gliomaLarotrectiniNeurotrophic tyrosine receptor kinase (NTRK)

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