CHOP-led network aims to unlock the genetic mysteries behind pediatric brain tumors

Unlocking the genetic mysteries behind pediatric brain tumors is at the heart of the mission of the Center for Data Driven Discovery in Biomedicine (D3b) at Children's Hospital of Philadelphia (CHOP). The Children's Brain Tumor Network (CBTN), a multi-institutional brain tumor research program with its operations center housed at D3b, has collected tumor samples from patients all over the world. Through funding from the Childhood Cancer Data Initiative of the National Cancer Institute (NCI), part of the National Institutes of Health (NIH), D3b will procure molecular characterization for thousands of these brain tumor samples providing an unprecedented level of insight into devastating cancers and paving the way for future therapeutic interventions.

Instead of a traditional monetary grant, the X01Sequencing & Genotyping Resource Access program provides critical NIH-supported resources that are needed for investigators to conduct their research. This program will support molecular characterization of more than 3,000 germline samples and more than 1,500 tumor samples across all pediatric brain tumor types that have been collected by D3b through CBTN since 2011. This characterization process will prioritize the most aggressive tumor types, supporting research for those cancers where there is a lack of existing data. Prior to the X01 program, approximately 1,000 of the more than 4,200 patient-derived specimens within the CBTN biobank housed at D3b have been characterized since 2017.

With molecular data derived from just a quarter of the research participants who've donated brain tumor tissue to date, CBTN has been able to support the launch of over 150 data science-based investigations. Now, with whole genome sequencing available for this entire cohort, the potential for new insights into the biology of childhood brain cancer cannot be overstated."

Adam Resnick, PhD, Co-Director of the D3b Center at CHOP and Scientific Co-Chair of CBTN

As childhood brain tumors are not common enough for any single research center to encounter enough patients with the same diagnosis to gather the amount of samples or data needed to conduct substantive research, collaborations like CBTN play a crucial role in advancing the pace of progress. The more data available to researchers, the higher the potential for novel insights that lead to breakthroughs in treatment.

"Childhood brain tumors represent some of the most challenging targets for biomedical research, due to the scarcity of molecular data available to make actionable discoveries," said Jay Storm, MD, Co-Director of the D3b Center, Chief of the Division of Neurosurgery at CHOP and a Principal Investigator of CBTN. "Through this partnership, the NCI/NIH and the Childhood Cancer Data Initiative have made possible a brand new era in research."

Data from this cohort of samples – generously provided by patients and their families over several years – will be made available alongside other cohorts that have been collected as part of NCI initiatives, including Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Pediatric MATCH (Molecular Analysis for Therapy Choice), as well as the NIH Common Fund's Gabriella Miller Kids First Pediatric Research Program (Kids First). Kids First is a collaborative pediatric research effort with the goal of understanding the genetic causes and links between childhood cancer and structural birth defects. Additionally, approximately 300 CBTN samples of diffuse midline glioma (DMG) and atypical teratoid rhabdoid tumor (ATRT) – two tumors that affect the central nervous system and the brain – will be characterized through a new partnership with the Count Me In Initiative.

The sequencing for this project is supported by the NCI Childhood Cancer Data initiative under award number 1X01CA267587-01, and will be performed at the Broad Institute of the Massachusetts Institute of Technology and Harvard University.