Decoding the Biology of Oligodendroglioma through a New Model for Collaboration

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Jonathan Waller

Brain and spinal cord tumors are the second most common cancers in children (after leukemia) and the leading cause of disease-related death in children in the US. They account for about 1 out of 4 childhood cancers. Oligodendroglioma (oligo) is a rare form of primary malignant brain and central nervous system (CNS) cancer diagnosed in roughly 1,500 people in the United States each year – and while they can develop at any age, are more often found in teens and young adults aged 15 and over. An estimated 15,000 people are living with this form of brain cancer in the United States today. Roughly 1 in 4 will succumb to their illness within 5 years of receiving a diagnosis.

Because of its rarity, access to high-quality oligo biospecimens and molecular data can be scarce. This has made oligodendroglioma a particularly difficult form of brain cancer for scientists to study, and movement toward improved treatments has been negligible.

However, a unique partnership between public agencies, patient foundations, and research institutions has been struck, forging a new model for pediatric cancer research and marking a new era in innovative therapeutic development for one of the rarest forms of brain/CNS cancer in children and adults.

Oligo Nation (ON), a non-profit focused on advancing translational medical research to improve treatments for oligo patients, has been a research partner with Children’s Brain Tumor Network (CBTN) since 2019. Together, the two organizations launched Project Open Oligo to define a new accelerated model for discovery, toward improved treatments for oligo patients.

This year Project Open Oligo expanded further – with ON accepting a large cohort of specimens from the Barrow Neurological Institute and CBTN’s operations center at Children’s Hospital of Philadelphia (CHOP) partnering with the University of Pennsylvania (UPenn) – to create a combined cohort of oligo specimens drawn from patients at a wide variety of age ranges and stages of diagnosis.

Initially, with sequencing support provided by Oligo Nation, the trio aimed to solely conduct whole genome and RNA sequencing on this collection of specimens. However, knowing that relying exclusively on genomics for diagnosis and treatment is insufficient, as the needs of many cancer patients remain unresolved, the group forged a collaboration with the National Cancer Institute (NCI)’s Clinical Proteomic Tumor Analysis Consortium (CPTAC) – pioneers in the clinical characterization of tumors using proteogenomic analysis.

“Proteogenomics” combines analysis of the proteins, genes, and RNA transcription involved in tumor development, which give a more complete understanding of the tumor. Studies on multiple forms of omic data such as these are growing in popularity since they allow scientists to investigate complex mechanisms across molecular layers. CPTAC has established standardized workflows that can produce detailed, reproducible, and measurable information from clinical specimens, which enhances data integration while conserving precious clinical samples.

Having established a strong relationship with CBTN through a collaboration on a landmark proteogenomics study in pediatric brain cancer published in Cell in 2020, and seeing the potential for groundbreaking new discoveries that such a large cohort of oligo subjects could provide, CPTAC will perform full proteomic data generation and proteogenomic data integration of each tumor sample provided by CBTN, ON, and UPenn. While the whole genome and RNA sequencing initially anticipated by Project Open Oligo would have yielded two forms of omic data for analysis, this collaboration with CPTAC will produce a more complete understanding of cancer biology and identify possible new therapeutic interventions that can be monitored by proteogenomic targeted testing into the clinical laboratory.

Anticipated data repositories are the CBTN’s Pediatric Brain Tumor Atlas for genomics data and NCI’s Proteomic Data Commons (in NCI’s Cancer Research Data Commons) for proteomics data.

When complete, this partnership will produce the largest and most molecularly annotated collection of oligodendroglioma data ever generated and shared with the public as a community resource. The implications for scientific discovery are tremendous.

“I am proud of this new collaboration as it extends our coordination with colleagues at CHOP, and most importantly, improves our understanding of rare cancers to possibly accelerate the development of more effective therapies so that all patients have the chance to live long and healthy lives,” said Dr. Henry Rodriguez, Director of the Office of Cancer Clinical Proteomics Research at NCI.

This new project will target the biology associated with IDH1 mutations and the biological associations between tumor progression/recurrence/treatment response. These data will ultimately integrate with existing CPTAC cohorts of brain cancer, especially high-grade gliomas, leveraging CPTAC’s adult cancer studies that include the largest and most detailed molecular characterization study of adult brain cancer to date (published in Cancer Cell in 2021).

“By gaining such a detailed molecular perspective on oligodendroglioma, we will soon have the resources needed to identify new therapeutic targets that could lead to a cure,” said Dr. Adam Resnick, Director of the Center for Data Driven Discovery in Biomedicine at CHOP and Co-Chair of the CBTN Scientific Committee.

“Not only is this collaboration an exciting new venture into biomedical research, but also a significant triumph for both the cancer and rare disease communities. Through this partnership between private foundations, research institutions, and government, a new course for innovative collaboration has been charted, and serves as a model for future discovery into rare illnesses in children and adults,” he concluded.