Review on Canine Oral Melanoma: An Undervalued Authentic Genetic Model of Human Oral Melanoma?

Oral melanoma (OM) is a highly aggressive tumor of the oral cavity in humans and dogs. Here we review the phenotypic similarities between the disease in these 2 species as the basis for the view that canine OM is a good model for the corresponding human disease. Utility of the "canine model" has likely been hindered by a paucity of information about the extent of the molecular genetic similarities between human and canine OMs. Current knowledge of the somatic alterations that underpin human tumorigenesis and metastatic progression is relatively limited, primarily due to the rarity of the disease in humans and consequent lack of opportunity for large-scale molecular analysis. The molecular genetic comparisons between human and canine OMs that have been completed indicate some overlap between the somatic mutation profiles of canine OMs and a subset of human OMs. However, further comparative studies featuring, in particular, larger numbers of human OMs are required to provide substantive evidence that canine OMs share mechanisms of tumorigenesis with at least a subset of human OMs. Future molecular genetic investigations of both human and canine OMs should investigate how primary tumors develop a metastatic gene expression signature and the genetic and epigenetic alterations specific to metastatic sites. Such studies may identify genetic alterations and pathways specific to the metastatic disease which could be targetable by new drugs.