Grant: Project Grant - Priority Announcement: Pediatric Cancer Research

Medulloblastoma accounts for ~20% of childhood brain cancers. Current treatment involves surgical removal, followed by chemotherapy or radiation therapy. Survivors often experience learning and memory problems because of these harsh treatments. Therefore there is a need to develop new medications that improve survival and survivors' quality of life. These cancers do not appear to be driven by simple genetic mutations. Rather, the cells of these tumours appear to be most similar to brain cells in a developing fetus, and a leading theory is that these tumours arise from a changed program in brain development. Our goal is to discover which developing brain cells these cancer cells are most similar to, and to see what changed between normal development and these tumours. By learning which brain cells tumours grow from, we will learn what programs make a cell in a baby brain cancerous. Once we know the nature of these changes, we can design drugs to rewrite or kill these cancerous programs specifically, leaving healthy cells in a patient's brain unaffected and reducing side effects. In this project, we will look at a type of programs used to control genes in brain cells, called DNA methylation. We will compare this programs in different groups of brain cells from post mortem developing brain, obtained from a tissue bank, and in tumour cells from patients. Because the brain is a complex mix of cells, and a tumour is a mix of cells as well, it is important to use methods that allow us to look at each cell separately. To use a fruit analogy, our techniques allow us to examine each fruit in a fruit salad, rather than looking at a smoothie. By doing this, we will be able to compare each cell type to tumours and identify which cell type the tumour is most similar to. Our project may identify novel cell programs that are changed in childhood brain cancer, that could be used to develop new medications to stop or reverse these cancers.