Grant: Project Grant

Cancer arises when a single cell acquires genetic alterations leading to uncontrolled replication. As tumour cells divide they continue to acquire genetic mutations which they pass on to their descendants, forming subpopulations with different characteristics. The ability of tumours to generate genetic diversity and evolve in response to selective pressures can enable them to develop resistance to treatment. Certain forms of large-scale genetic alteration have been associated with poor patient survival in multiple cancer types, and are common in ovarian cancer. Understanding the frequency with which these alterations arise within tumours and the diversity they generate requires profiling the genetic material of individual cancer cells. We will optimize experimental approaches for sequencing the genetic material of single tumour cells and develop computational methods to characterize cellular diversity. We will then apply these methods to profile the composition of tissue donated by high grade serous ovarian cancer (HGSOC) patients at initial diagnosis and following relapse. The five-year survival rate for ovarian cancer patients in Canada is currently 44%. Many patients initially respond to treatment, but subsequently develop resistance and experience disease recurrence. This study will help define patterns of mutation associated with ovarian cancer progression, with potential to identify new prognostic markers and targets for drug development.