Project 467174

Synovial sarcoma is a soft-tissue malignancythat mainly affects adolescents and young adults. Unfortunately, standard chemotherapeutics do not increase survival, creating a need for targeted therapies. Synovial sarcoma cells have a unique DNA mutation that creates an altered protein which causes cancerous growth. This mutated protein changes the accessibility of certain regions of a cells DNA, changing many cellular functions, such as how the cell makes proteins required to carry out tasks. Currently, the development of new treatments is being held back because we do not know exactly how or where the important DNA changes are taking place. Recently, through analysis of the accessible DNA regions in single cells from patient synovial sarcomas, our lab has identified a distinct type of malignant cell present in all tested synovial sarcoma tumours, which we believe represents the key self-renewing population within synovial sarcoma that resists chemotherapy. My research will build on this novel finding by expanding the dataset to include information on the DNA accessibility and gene expression of individual cells for 30 tumour samples from Vancouver and Toronto. Using this data, I will determine how the DNA accessibility and gene expression is different in the identified group compared to the bulk of the tumour. I will use new methods to trace changes in individual cells within a tumour to figure out how the mutant protein affects the cancer cell throughout tumour progression. By understanding how the mutant protein changes the way our cells can access our DNA, I hope to identify new and effective ways that we can treat synovial sarcoma patients.