Translating Genomic Discoveries to Cure Ultrahypermutant Mismatch Repair Deficient Brain Tumours
Malignant brain tumours are the most common cause of death among children with cancer, but there is no known cure. This project will advance research in this important field. Inherited mutations and childhood cancer Many children with malignant brain tumours inherit mutations that are responsible for the tumour's development. Using this knowledge, the research team established an international consortium to study children with biallelic mutations in mismatch repair genes (termed bMMRD). The team recently discovered that bMMRD malignant brain tumours have the highest mutation burden of all cancers. This finding will be used to study the causes, prevention, and treatment options for brain tumours. Project objectives More specifically, this project aims to: -elucidate the effect of mutation accumulation on cell fitness and cancer progression -identify genes which are key for these processes -develop novel therapies based on these alterations -design and implement an international study to screen targeted preventive and therapeutic compounds for pre-clinical testing -use the findings to identify directions for developing new diagnostic and therapeutic tools for the clinical care of children and adults in low- and high-income settings -further develop the training environment and research collaboration among consortium partners Insights into brain cancer Once completed, this project will open the window to understanding basic cancer processes. This will enable the development of new therapies. The knowledge will also support a committed international group of clinicians and scientists to treat more common malignant brain tumours among adults. Project leadership The project lead is Uri Tabori at the Hospital for Sick Children, Toronto, Canada. His collaborators include: -Gideon Rechavi, Tel Aviv University, Israel -Fatiha Gachi, Mustapha Bâcha Hospital, Algeria -Andrea Cappellano, Federal University of São Paulo, Brazil -Shadi Fadel at Alexandria Faculty of Medicine, Alexandria University, Egypt -Brijesh Arora,Tata Memorial Centre, India -Nisreen Amayiri, King Hussein Cancer Center, Jordan Project funding This project is funded through the first research competition of the Joint Canada-Israel Health Research Initiative. The Initiative is a collaboration between the Azrieli Foundation, the Canadian Institutes of Health Research, the Israel Science Foundation, and Canada's International Development Research Centre.