TY  - JOUR
AU  - Arora, Sonali
AU  - Nuechterlein, Nicholas
AU  - Jensen, Matt
AU  - Glatzer, Gregory
AU  - Sievers, Philipp
AU  - Varadharajan, Srinidhi
AU  - Korshunov, Andrey
AU  - Sahm, Felix
AU  - Mack, Stephen C
AU  - Taylor, Michael D
AU  - Gujral, Taran
AU  - Holland, Eric C
TI  - Integrated transcriptomic landscape of medulloblastoma and ependymoma reveals novel tumor subtype-specific biology.
JO  - Neuro-Oncology
VL  - nn
SN  - 1522-8517
CY  - Oxford
PB  - Oxford Univ. Press
M1  - DKFZ-2025-02237
SP  - nn
PY  - 2025
N1  - epub
AB  - 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.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.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 SHH tumors by patient age. We also identified subtype-specific pathways and gene fusions, enriched in each group.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.
KW  - RNA-Seq (Other)
KW  - copy number (Other)
KW  - gene fusions (Other)
KW  - pathways (Other)
KW  - subtyping (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:41159380
DO  - DOI:10.1093/neuonc/noaf251
UR  - https://inrepo02.dkfz.de/record/305575
ER  -