Glioblastoma brain cancer, CT scan

In what is being described as a first-of-its-kind research platform, researchers from Children’s Hospital of Philadelphia (CHOP) and more than 20 other foundations and organizations have released an open-source analysis platform for pediatric brain tumors for identifying genetic variants that could help fuel diagnostic and therapeutic research and development.

Others involved in the development of the research tool include the Alex’s Lemonade Stand Foundation Childhood Cancer Data Lab, the Children’s Brain Tumor Network (CBTN) and the Pacific Pediatric Neuro-Oncology Consortium (PNOC). Details of the platform were published today in the journal Cell Genomics.

Work on the data resource stretches back a dozen years to 2011, when CBTN and PNOC began preparing what is now nearly 6,000 tumor samples ad 68,000 sub-samples. Of these, more than 1,000 tumors were sequenced to create the Pediatric Brain Tumor Atlas (PBTA), initially released in 2018. Researchers have since used this data to search for which genetic variants may be the drivers of particular types of brain cancer. Now, with the support of the Alex’s Lemonade Stand Foundation Childhood Cancer Data Lab, the team built an open-source version called OpenPBTA.

“While there have been many proponents of an open-source model for scientific research, nothing like this existed for pediatric cancer,” said Jo Lynne Rokita, PhD, a supervisory bioinformatics scientist leading OpenPBTA at the Center for Data-Driven Discovery (D3B) at CHOP and one of the study’s corresponding authors. “We designed OpenPBTA so that anyone could access the data, contribute to its analysis, and/or use it in their own research.”

OpenPBTA is available to any researcher who is looking for new potential therapeutic targets or to translate their researcher into the clinic, by providing an open real-time framework to genomically characterize pediatric brain tumors. According to the collaborators, it is the first large-scale cloud-based genomic data resource of its kind.

“Collaboration is key to accelerating new cure discovery. OpenPBTA made it possible for experts across the globe to come together and gain a deeper understanding of the leading cause of cancer-related death in children and young adults,” said Jay Scott, co-executive director of Alex’s Lemonade Stand Foundation.

In the study published today, the research partners demonstrate how it can be used to deepen the understanding of potential drivers of pediatric cancers. In the report, the investigators demonstrate how the loss of the tumor suppressor gene TP53 serves as a biomarker indicating poor survival in ependymomas and certain diffuse midline gliomas—fast-growing tumors of the brain and spinal cord—and that dysregulation of the gene was also implicated in hypermutant high-grade gliomas.

“Solving pediatric brain tumors cannot be accomplished by any one institution. The OpenPBTA model of shared, real-time collaboration supported by PNOC and CBTN has not only empowered new discoveries, but also innovative ways of performing the required science on behalf of accelerated, collaborative innovation for children affected by brain tumors,” said Sabine Mueller MD, PhD, of the University of California, San Francisco, the Lead of PNOC, and executive co-chair of CBTN.

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