Enabling precision oncology of sarcomas in Canada

Project goals:

1. Genomics and epigenomic characterization of synovial sarcomas
2. Expansion to a broader range of sarcoma subtypes with known alterations in epigenetic modifiers

Summary:

Sarcomas are a group of more than 60 cancer types arising from the bones and connective tissues in the body, and mostly affect adolescents and young adults, half of whom will die from the disease. There is an urgent, unmet need to identify new and effective treatments for people with sarcomas. To do that, we first need to understand what drives these cancers. Many cancers harbour multiple DNA sequence mutations that work together to change a normal cell into cancer. However, several sarcoma types appear to have just a single DNA sequence mutation that somehow causes widespread changes to DNA structure, called the “epigenome”, that is still enough to convert a normal cell into cancer. Sarcoma types such as synovial sarcoma, chondrosarcoma and chordoma each have different single mutations that are believed to affect the epigenome (DNA structure). Our team proposes to use newly available technologies to create a comprehensive picture of not only the DNA mutations but also the changes to DNA structure in several types of sarcomas which we believe will allow us to identify new treatment strategies. This is especially timely as there are recently developed epigenome-targeting drugs that can restore a more normal DNA structure. Once our research workflow is established with three initial sarcoma types, we intend to expand our research into additional sarcoma subtypes that are suspected to also be driven by changes to the epigenome.

Our proposal builds on strong existing local, national and international collaborations amongst Canada’s top sarcoma researchers. Leadership for this proposal at BC Cancer is enabled through an established collaboration between Drs. Nielsen and Hirst who bring extensive and complementary expertise in clinical and scientific research. This expertise is complemented and extended nationally through collaboration with Drs. Andrulis and Wunder at the University of Toronto.