Language

English

Publication Date

2-1-2026

Journal

Neuro-Oncology

DOI

10.1093/neuonc/noaf251

PMID

41159380

PMCID

PMC12979040

Abstract

Background: Medulloblastoma and ependymoma are common pediatric central nervous system tumors with significant molecular and clinical heterogeneity. While molecular subgrouping has enabled classification into molecular subtypes, the extent of heterogeneity within these subgroups remains poorly defined.

Methods: We collected bulk RNA sequencing data from 888 medulloblastoma and 370 ependymoma tumors to establish a comprehensive reference landscape. After rigorous batch effect correction, normalization, and dimensionality reduction, we generated a unified landscape to explore gene expression, signaling pathways, RNA fusions, and copy number variations.

Results: Our transcriptional analysis revealed distinct clustering patterns, including two primary ependymoma compartments, EPN-E1 and EPN-E2, each with specific RNA fusions and molecular signatures. In medulloblastoma, we observed precise stratification of Group 3/4 tumors by subtype and in Sonic Hedgehog (SHH) tumors by patient age. We also identified subtype-specific pathways and gene fusions, enriched in each group.

Conclusions: This transcriptomic landscape serves as a resource for biomarker discovery, diagnostic refinement, and prediction of tumor biology and outcome. By enabling projection of new patients' bulk RNA-seq data onto the reference map using nearest neighbor analysis, the framework supports accurate subtype classification. The landscape is publicly available via Oncoscape, an interactive platform for global exploration and application.

Keywords

Humans, Medulloblastoma, Ependymoma, Transcriptome, Cerebellar Neoplasms, Biomarkers, Tumor, Child, Gene Expression Profiling, DNA Copy Number Variations, Female, Male, Child, Preschool, Prognosis, Gene Expression Regulation, Neoplastic, Adolescent, copy number, gene fusions, pathways, RNA-Seq, subtyping, RNA-Seq, copy number, gene fusions, pathways, subtyping

Published Open-Access

yes

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