PNNL

Abstract

We report a comprehensive proteogenomic analysis, including whole genome sequencing, RNA sequencing, proteomic and phosphoproteomic profiling, of 218 tumors across seven histologic types of childhood brain cancer. Proteomic data identifies common biological themes that span histologic boundaries, suggesting that treatments used for one histologic type may be applied effectively to other tumors sharing similar proteomic features. Immune landscape characterization reveals diverse tumor microenvironments across and within diagnoses. Proteomic data further reveal functional impacts of somatic mutations and CNVs not evident in transcriptomic data alone. Kinase-substrate association and coexpression network analysis identifies important biological mechanisms of tumorigenesis. Survival analysis of high grade glioma tumors without H3K27M mutation points to the prognostic value of IDH proteins. This is the first largescale proteogenomic analysis across traditional histologic boundaries to uncover foundational pediatric brain tumor biology and inform rational treatment selection.