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Integrated transcriptomic landscape of medulloblastoma and ependymoma reveals novel tumor subtype-specific biology

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 defin...

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Detalles Bibliográficos
Autores principales: Arora, Sonali (Autor) , Nuechterlein, Nicholas (Autor) , Jensen, Matt (Autor) , Glatzer, Gregory (Autor) , Sievers, Philipp (Autor) , Varadharajan, Srinidhi (Autor) , Korshunov, Andrey (Autor) , Sahm, Felix (Autor) , Mack, Stephen C. (Autor) , Taylor, Michael D. (Autor) , Gujral, Taranjit S. (Autor) , Holland, Eric C. (Autor)
Formato: Article (Journal)
Lenguaje:inglés
Publicado: 2026
In: Neuro-Oncology
Year: 2026, Volumen: 28, Número: 2, Pages: 505-519
ISSN:1523-5866
DOI:10.1093/neuonc/noaf251
Acceso en línea:Verlag, kostenfrei, Volltext: https://doi.org/10.1093/neuonc/noaf251
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Notas de Autor:Sonali Arora, Nicholas Nuechterlein, Matt Jensen, Gregory Glatzer, Philipp Sievers, Srinidhi Varadharajan, Andrey Korshunov, Felix Sahm, Stephen C. Mack, Michael D. Taylor, Taranjit S. Gujral, and Eric C. Holland
Descripción
Sumario: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.
Notas:Online veröffentlicht am 24. Oktober 2025
Gesehen am 27.05.2026
Descripción Física:Online Resource
ISSN:1523-5866
DOI:10.1093/neuonc/noaf251

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