OpenPBTA: The Open Pediatric Brain Tumor Atlas

Area of Science:

• Oncology
• Genomics
• Bioinformatics

Background:

• Pediatric brain and spinal cancers represent the primary disease-related cause of mortality in children.
• The urgent need for effective therapeutic strategies necessitates accelerated discovery processes.
• Collaborative initiatives are crucial for advancing pediatric oncology research.

Purpose of the Study:

• To establish a comprehensive genomic characterization of pediatric brain tumors.
• To create an open, collaborative platform for data sharing and analysis.
• To identify key genomic alterations associated with specific pediatric brain tumor subtypes and patient outcomes.

Main Methods:

• Systematic tumor biobanking, model generation, and sequencing by the Children's Brain Tumor Network (CBTN) and Pacific Pediatric Neuro-Oncology Consortium (PNOC).
• Development of OpenPBTA, an open collaborative project utilizing over 40 scalable analysis modules.
• Genomic characterization of 1,074 pediatric brain tumors.

Main Results:

• Transcriptomic classification identified universal TP53 dysregulation in mismatch repair-deficient hypermutant high-grade gliomas.
• TP53 loss was identified as a significant negative prognostic marker for overall survival in ependymomas and H3 K28-mutant diffuse midline gliomas.
• The OpenPBTA platform provides harmonized genomic data for over 1,000 pediatric brain tumors.

Conclusions:

• OpenPBTA serves as a valuable resource for the pediatric oncology community, accelerating research and discovery.
• The identified genomic alterations provide insights into tumor biology and potential therapeutic targets.
• The platform is actively being applied to other pediatric cancers and informs molecular tumor board decision-making.