EPCO-59. INTEGRATED MULTI-OMIC PROFILING REVEALS PROTEOMIC HETEROGENEITY AND PATHWAY DYNAMICS IN MEDULLOBLASTOMA

Abstract Medulloblastoma (MB), a common malignant pediatric brain tumor, presents significant treatment challenges due to molecular heterogeneity and limited targetable genomic alterations. Proteomics offers unique insights into tumor biology beyond genomic classifications, yet comprehensive proteomic characterization of pediatric brain tumors remains limited. In this study, we established a multi-omic cohort of 166 primary medulloblastoma tumors collected through an institutional clinical trial. We integrated deep mass spectrometry-based proteomics (median 13,921 proteins detected per sample) and phosphoproteomics with matched DNA methylation, whole exome sequencing, and RNA sequencing data. Proteomic profiling identified distinct molecular signatures across subgroups, and their integration with driver gene mutations revealed subgroup-specific pathway alterations. Non-negative matrix factorization and cross-layer correlation analyses identified regulatory discordances and post-transcriptional regulation in tumor pathways, while network analysis characterized hub proteins driving subgroup-specific signaling cascades. This comprehensive multi-omic dataset represents one of the largest integrated proteomic resources for pediatric brain tumors, revealing differential RNA-protein correlations and developmental pathway signatures in MB subgroups. The resource establishes a foundation for understanding MB biology and identifying proteomic drivers of tumor progression and treatment response.