Researchers from Children’s Hospital of Philadelphia (CHOP), the Alex’s Lemonade Stand Foundation Childhood Cancer Data Lab, the Children’s Brain Tumour Network (CBTN), the Pacific Paediatric Neuro-Oncology Consortium (PNOC), and more than 20 additional institutions have partnered to create a first-of-its-kind open-source, reproducible analysis platform for paediatric brain tumours.

With the help of thousands of genomically sequenced samples, researchers have used this platform to identify initial findings about genetic variants associated with poorer outcomes that could help guide future diagnostic and therapeutic advances.

The details of the platform and those initial findings were published online today by the journal Cell Genomics.

Paediatric brain tumours are collectively the leading cause of cancer-related death in children in the United States.

However, the severity of paediatric brain tumours varies wildly, with some having an almost universally fatal prognosis while others have relatively strong long-term survival rates, though all brain tumours negatively impact these children and their families to at least some degree.

Limited access to tissue samples and patient-derived cell lines has been a significant barrier to understanding the differences between paediatric brain tumours at a molecular level.

That long sought-after data could lead to better diagnostic techniques and potential targeted therapies that could treat these deadly tumours.

In 2011, CBTN and PNOC began extracting and preparing what has now become nearly 6,000 tumour samples with over 68,000 sub-samples.

More than 1,000 of these tumours were sequenced to form the initial release of the Paediatric Brain Tumour Atlas (PTBA) in 2018, and data were made available without embargo so that researchers could study what variants might be driving certain types of brain tumours.

With the help of the Alex’s Lemonade Stand Foundation Childhood Cancer Data Lab, the team of researchers was able to build an open-source version of this atlas, the Open Paediatric Brain Tumour Atlas (OpenPBTA), to analyse these data. 

OpenPBTA is accessible to anyone conducting research who is looking for new therapeutic targets or finding new ways to translate research into clinical practice.

At the time of this study, OpenPBTA contained genomic and clinical data from more than 1,000 paediatric brain tumours and 22 patient-derived cell lines from the CBTN and PNOC.

The OpenPBTA provides an open, real-time framework to genomically characterise paediatric brain tumours.

It is the first large-scale, collaborative, open analysis of genomic data and provides a cloud-based resource for researchers looking for more comprehensive data on paediatric brain tumours.

“While there have been many proponents of an open-source model for scientific research, nothing like this existed for paediatric 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.”

“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.

Jaclyn N Taroni, PhD, another corresponding author on the study and Director of Alex’s Lemonade Stand Foundation Childhood Cancer Data Lab, said, “With our successful launch of OpenPBTA, we’re hoping the research community adapts this model to other paediatric cancers.”

OpenPBTA is already providing researchers with more insight into potential drivers of paediatric brain tumours.

In this study, researchers found that the loss of the tumour suppressor gene TP53 is a significant marker for poor overall survival in fast-growing brain and spinal cord tumours called ependymomas and certain diffuse midline gliomas, and dysregulation of the gene was also implicated in hyper mutant high-grade gliomas.

“Solving paediatric brain tumours 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 tumours," said Sabine Mueller MD, PhD, MAS, Professor of Neurology, Neurosurgery and Paediatrics at the University of California, San Francisco, and the Lead of PNOC and executive co-chair of CBTN.

Article: OpenPBTA: An open paediatric brain tumour atlas

Source: Children's Hospital of Philadelphia