Transcriptomic landscape identifies two unrecognized ependymoma subtypes and novel pathways in medulloblastoma

Abstract

Medulloblastoma and ependymoma are prevalent pediatric central nervous system tumors with significant molecular and clinical heterogeneity. We collected bulk RNA sequencing data from 888 medulloblastoma and 370 ependymoma tumors to establish a comprehensive reference landscape. Following rigorous batch effect correction, normalization, and dimensionality reduction, we constructed a unified landscape to explore gene expression, signaling pathways, gene fusions, and copy number variations. Our analysis revealed distinct clustering patterns, including two primary ependymoma compartments, EPN-E1 and EPN-E2, each with specific gene fusions and molecular signatures. In medulloblastoma, we achieved precise stratification of Group 3/4 tumors by subtype and in SHH tumors by patient age. Our landscape serves as a vital resource for identifying biomarkers, refining diagnoses, and enables the mapping of new patients' bulk RNA-seq data onto the reference framework to facilitate accurate disease subtype identification. The landscape is accessible via Oncoscape, an interactive platform, empowering global exploration and application.