Using Comparative Genomics to Leverage Animal Models in the Identification of Cancer Genes. Examples in Prostate Cancer

Abstract

The identification of cancer biomarkers that will predict susceptibility to disease and subsequent clinical outcome are key components of future genomics-based tailored medical care. Animal models of disease provide a rich resource for the identification of potential cancer biomarkers. Animal models of prostate cancer in particular offer the potential to identify cancer genes associated with dietary and environmental factors. The key issue is the timely and efficient identification of candidate genes that are likely to impact on human prostate cancer. Here, we demonstrate comparative genomics-based methods for the identification of candidate genes in animal models that are associated with human chromosomal regions implicated in prostate cancer. Using publicly available bioinformatics tools, comparisons can be made between cancer-specific datasets, genomic sequencing data and cross-species comparative maps to identify potential cancer biomarkers. This process is demonstrated by using rat models of prostate cancer to identify candidate human prostate cancer genes. Genes identified through these techniques can be screened as biomarkers for response to chemopreventive agents, as well as being used in transgenic or knockout mice to engineer better animal models of human prostate cancer. The bioinformatics techniques outlined here can be used to leverage genomic data from any animal cancer model for use in the study and treatment of human cancer.