Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

Cancer is driven by mutations in the genome that accumulate over the course of lifetime. Some of these mutations are harmful and drive the progression of cancer while others are tolerated without damage to cells and tissues. To distinguish between these mutations, we look for patterns of mutational recurrence across a population, determine whether they are present in the healthy population and design strategies to predict their impact on biological function based on established knowledge. Small mutations involving changes to several bases of DNA are becoming easier to characterize using enhanced sequencing technology and computer algorithms but large rearrangements of the genome still present a problem in every step of the pipeline. Yet, genomic rearrangements are the predominant mutation type in almost half of all cancers, leaving the resolution of these challenges both poignant and pressing. Currently, several technologies are improving the cost and accuracy of the detection of genomic rearrangements while the recent assemblies of the 3-dimensional genome are improving our knowledge of their functional impact. Our lab is part of the largest collaboratory to date for the analysis of cancer genomes and have contributed several algorithms for the purpose of identifying recurrent small mutations which drive cancer. We propose to take this opportune time to develop a new method for the prioritization of genomic rearrangements. Using some of the largest collections of cancer genomes, we will examine both molecular and clinical correlates of genomic rearrangements, identifying associated changes in cell biology and clinical presentation. We aim to present a logical progression of how these molecular features lead to better or worse outcomes. The ultimate purpose of our research is to improve clinical practice based on molecular features of tumours.