Grant: CIHR Fellowship

Annually, approximately 200 Canadian children with glioblastoma, a rare type of brain cancer, will die of their disease. If these kids are given standard treatment they will only survive 12- 14 months, therefore new treatment options are urgently needed. A rare bone cancer, called giant cell tumours of the bone are often benign, however can be aggressive resulting in lung metastasis. In these two tumour types, the same histone 3.3 gene is mutated. This occurs in 40% of childhood brain cancers and in over 90% of giant cell tumours of the bone. Histones are guardians of the genome, as they are proteins that package DNA, enabling it to be folded tightly together into the nucleus. The mutations identified in the gene histone 3.3, affect the epigenetics, (epi- over or on top of), which implies altering how genes are expressed without changing the DNA sequence. To also determine how mutations identified in two tumour types affect the epigenetics of the cell, we will use a new technique called Hi-C to determine the 3D structure of DNA. This analysis will give us insight into how the same mutations in different tumour types may change the structure and organization of the cell nucleus, giving us clues into how cells become cancerous. This important research will provide new information on the biology of these deadly brain tumours and rare bone tumours, and also lead to new targets for novel therapeutics. My research will not only help Canadian children, but will positively affect children with brain cancer from all over the world. The ultimate goal of this project is to understand how these mutations cause cancer, which may provide better treatment options for both rare tumour types and some hope for surviving these dreadful cancers.