OpenPBTA: An Open Pediatric Brain Tumor Atlas

Abstract

Pediatric brain and spinal cancer are the leading disease-related cause of death in children, thus we urgently need curative therapeutic strategies for these tumors. To accelerate such discoveries, the Children's Brain Tumor Network and Pacific Pediatric Neuro-Oncology Consortium created a systematic process for tumor biobanking, model generation, and sequencing with immediate access to harmonized data. We leverage these data to create OpenPBTA, an open collaborative project which establishes over 40 scalable analysis modules to genomically characterize 1,074 pediatric brain tumors. Transcriptomic classification reveals that TP53 loss is a significant marker for poor overall survival in ependymomas and H3 K28-altered diffuse midline gliomas and further identifies universal TP53 dysregulation in mismatch repair-deficient hypermutant high-grade gliomas. OpenPBTA is a foundational analysis platform actively being applied to other pediatric cancers and inform molecular tumor board decision-making, making it an invaluable resource to the pediatric oncology community.

Competing Interest Statement

Casey S. Greene's spouse was an employee of Alex's Lemonade Stand Foundation, which was a sponsor of this research. Joshua A. Shapiro, Candace L. Savonen, Chante J. Bethell, Stephanie J. Spielman, and Jaclyn N. Taroni are or were employees of Alex's Lemonade Stand Foundation, a sponsor of this research. Angela J. Waanders is a member of the Scientific Advisory boards for Alexion and DayOne Biopharmaceuticals.

Footnotes

* https://doi.org/10.5281/zenodo.7044566

* https://github.com/AlexsLemonade/OpenPBTA-analysis

* https://github.com/AlexsLemonade/OpenPBTA-manuscript/