Integrated Proteogenomic Characterization across Major Histological Types of Pediatric Brain Cancer

Children's Brain Tumor Network, Clinical Proteomic Tumor Analysis Consortium

Research output: Contribution to journalArticlepeer-review

Abstract

We report a comprehensive proteogenomics analysis, including whole-genome sequencing, RNA sequencing, and proteomics and phosphoproteomics profiling, of 218 tumors across 7 histological types of childhood brain cancer: low-grade glioma (n = 93), ependymoma (32), high-grade glioma (25), medulloblastoma (22), ganglioglioma (18), craniopharyngioma (16), and atypical teratoid rhabdoid tumor (12). Proteomics data identify common biological themes that span histological boundaries, suggesting that treatments used for one histological type may be applied effectively to other tumors sharing similar proteomics features. Immune landscape characterization reveals diverse tumor microenvironments across and within diagnoses. Proteomics data further reveal functional effects of somatic mutations and copy number variations (CNVs) not evident in transcriptomics data. Kinase-substrate association and co-expression network analysis identify important biological mechanisms of tumorigenesis. This is the first large-scale proteogenomics analysis across traditional histological boundaries to uncover foundational pediatric brain tumor biology and inform rational treatment selection.

Original languageEnglish (US)
Pages (from-to)1962-1985.e31
JournalCell
Volume183
Issue number7
DOIs
StatePublished - Dec 23 2020

Keywords

  • BRAF alteration
  • CPTAC
  • CTNNB1 mutation
  • kinase activity score
  • kinase substrate regulation
  • pediatric brain tumor
  • post-translational modification
  • proteomic cluster
  • recurrent versus primary tumors
  • tumor microenvironment

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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