Naturally occurring cancers in dogs: insights for translational genetics and medicine

Here, we briefly review the state of knowledge of human cancer genetics to elaborate on the need for different types of mammalian models, highlighting the strengths of the dog. Mouse models are unparalleled for their experimental tractability and rapid genetic manipulation but have some key limitations in the area of human relevance. Companion dog models are attractive, because they are genetically more similar to humans, share environmental exposures with their owners, suffer from the same diseases as humans, and receive a high level of health care. They are ideal for the study of chronic diseases, because they age five to eight times faster than humans and generally live to old age. In addition, each dog breed is on the order of 100-fold genetically simpler than the whole human or dog population. These traits make the dog ideal for the study of complex genetics of naturally occurring cancers. Here, we contrast the relative strengths of cancer genetics in humans and dogs. We propose that humans are most ideal for the study of somatic cancer genetics, whereas dogs are most ideal for germline genetics. That proposition is supported by comparison of genome-wide association studies (GWASs) in human and canine cancer. One of the advantages of dog cancer GWASs is the ability to rapidly map complex traits, conduct fine mapping and identification of causative variation, and thus be in a position to move on to functional studies. We mention how these strengths of dog models will lead to rapid advances in translational medicine.