Surveying the Human Genome for Genetic Markers Associated with the Mutator Phenotype and Chromosomal Instability

Cancer is a genetic disease that develops as a result of the acquisition of stable somatic mutations. Many cancers are believed to acquire mutations at significantly increased rates, a state commonly referred to as the "mutator phenotype". In this study, I utilize whole genome sequencing data available from the ICGC Pancreatic Cancer Sequencing Initiative (PCSI) and PanCancer Analysis of Whole Genomes (PCAWG) projects to identify genes that may be associated with chromosomal instability or mutator phenotypes. I have found two novel candidate genes (XIRP2 and STARD9) that appear to increase the accumulation of double-stranded breaks in pancreatic cancer. Additionally, 15 candidate genes are identified across the PanCancer data set that increase the rate of accumulation of simple somatic mutations. Finally, I have also developed a novel non-parametric method for cancer driver discovery through the identification of mutations distributed uniformly across samples relative to differing background mutation rates.M.Sc