Assessing the Role of Copy Number Variants in Prostate Cancer Risk and Progression Using a Novel Genome-Wide Screening Method

Individual copy number variations in the genome may play a substantial role in influencing trait variation, yet due to technical limitations they have been understudied, and little is known about this new class of variant, including their distribution in most human populations and impact on common diseases. The goal of the current research is to screen the autosomal genome for these variants in constitutional DNA to assess their role in risk of development of prostate cancer and then evaluate any direct effect on the prostate. Using an array-based method we have identified heritable copy number variable regions that significantly differ between prostate cancer cases and controls of Mexican American origin. We have developed and conducted independent assays to analyze and validate CNVs identified using the array-based method and have validated 8 of 8 attempted. We have determined that a gene set comprised of genes in these CNV regions is statistically enriched for genes shown to be differentially expressed in prostate tumor and normal tissue. This supports our hypothesis that heritable structural variation may affect risk for PCa andor its progression.