High-grade brain tumours have a devastating impact on patients and families and are a huge burden on health care systems. For some patients, the diagnosis of a high-grade brain tumor can unfortunately be grim due to the limited treatment options available, while survivors often suffer from serious health issues post-treatment leading to a poor quality of life.

All brain tumours have distinct genetic alterations and changes in the way their DNA is organized (chromatin architecture). We are yet to fully understand what these changes represent and how they may be effectively targeted. However, prior research suggests that a better understanding of the function of chromatin changes, as well as how tumor cells communicate with each other and their surrounding environment, is crucial for the development of better treatment options.

This project aims to investigate how cancerous brain cells manipulate their chromatin architecture and how these changes are influenced by their immediate surroundings. This work will help us understand what sustains these abnormal structures and identify communication pathways within the tumor that can be disrupted with therapy to effectively target tumor cells. Ultimately, the knowledge acquired from this work will inform the development of targeted and effective treatments for patients with high-grade brain tumours.

While the current project focuses exclusively on brain tumours, it is possible for the methodology to be applied to other childhood, adolescent and young adult cancers in the future, as most similarly rely on co-opting developmental chromatin structures and neighbourhood for tumor formation and maintenance.

In addition to the development of new research capacity in Canada for the investigation of 3D and 4D chromatin architecture the proposed work will result in the development of:

• The bioinformatic infrastructure to analyze data from these types of studies
• Pathways for the sharing of material, expertise and data
• Research collaborations as possible targets are identified that could translate into further proteomic and clinical studies.