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Gliomas pediátricos con reordenamiento NTRK: un análisis clinicopatológico y molecular de seis casos

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

Abstracto

Aims:

Neurotrophic tyrosine receptor kinase (NTRK) gene fusions, although present in fewer than 2 % of gliomas, are recognized oncogenic drivers. With the approval of NTRK-targeted therapies, increasing attention has focused on these tumors, as targeted treatments may substantially enhance outcomes. This study aimed to characterize the pathological features and molecular diversity of pediatric NTRK-rearranged gliomas to inform targeted therapeutic strategies.

Methods And Results:

We analyzed six pediatric gliomas harboring NTRK fusions, identified through next-generation DNA sequencing (n = 5) and fluorescence in situ hybridization (n = 6). All tumors were supratentorial, involving the cerebral hemispheres (n = 3), thalamus (n = 2), and pineal region (n = 1). All infantile cases (n = 3) demonstrated high-grade histology and predominantly involved NTRK1, with one NTRK3 fusion. The three low-grade gliomas included two with NTRK1 and one with NTRK2 rearrangement. Dual gene fusions were identified in one case with intrachromosomal BCAN exon 14-NTRK1 exon 11 and NTRK1 exon 8-ARHGEF11 exon 2 rearrangements. One case harbored triple gene fusions, including interchromosomal ETV6-NTRK3 and PHYH-ETV6 fusions and an intrachromosomal NTRK3 rearrangement. Additional genetic alterations were detected in three cases, involving CDKN2A/B, TP53, ROS1, ABL1, MSH2, ARID4A, and CHEK1. DNA methylation profiling showed no collective methylation class and low-confidence matches to established methylation families.

Conclusion:

This study expands the clinicopathological and molecular spectrum of pediatric NTRK-rearranged gliomas, including rare entities and complex fusion patterns, and supports routine NTRK testing in pediatric gliomas irrespective of histological grade.

Palabras clave:

perfil de metilación de ADN Glioma Glioma hemisférico tipo infantil Larotrectinib Tirosina quinasa receptora neurotrófica (NTRK)

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