The Role of DNA Damage Sensing Genes in Genetic Instability and Radioresponse in Prostate Cancer

Prostate cancer (PCa) is the second cancer-related mortality cause in North American men. Despite the use of clinical prognostic factors, 20-60% of localized PCa fail primary local treatment. There is need for biomarkers that can guide primary treatment decisions or identify patients that need treatment intensifications. I have hypothesized that localized PCa is associated with an altered DNA damage response (DDR), which in turn can lead to genomic instability and affect the response to radiotherapy. Using array comparative genomic hybridization I have determined the frequency and prognostic importance of copy-number alterations (CNAs) in the main sensors of the DDR. I have shown that CNAs in these loci correlate with tumour genomic instability. The main finding is that Nibrin gains are a significant predictor of outcome following treatment with radiotherapy, but not surgery. NBN gains may be the first PCa predictive biomarker to facilitate local treatment decisions using precision medicine approaches.M.Sc