Single cell methods for characterizing genomic alterations in cancer

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 distinct 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 genetic alteration have been associated with poor patient survival in high grade serous 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 single tumour cells and develop computational and statistical methods to characterize this genetic diversity. This will provide researchers with new tools with which to study the mechanisms that underlie treatment resistance and patient relapse, and open the door for the development of new prognostic measures and therapeutic approaches.