Molecular Mechanisms of Canine Cancers

Abstract

Cancer is the leading cause of death in dogs, and 50 percent of dogs over the age of 10 develop cancer at some point. The most common cancers in dogs include lymphoma, mast cell tumors, osteosarcoma, mammary gland tumors, and melanoma, and many of them share marked similarities with their human counterparts. Although canines are afflicted with many of the same types of cancers as humans, the genetic basis behind these cancers are not as well understood. Thus, the aim of this study is to elucidate some of the molecular mechanisms behind canine cancers. Canine lymphoma mutation patterns generally vary with the type of lymphoma afflicted-B-cell lymphomas have mutations in the alternative NF-kB pathway including MAP3K14, whereas in T-cell lymphomas the mTOR pathway in boxers and cellular metabolism genes in golden retrievers are affected. Mast cell tumors are largely traced to internal tandem duplications and deletions in the juxtamembrane domain of the proto-oncogene c-KIT. In osteosarcoma, mutations in RB1 and TP53 (especially G: C->A:T transitions in exons 4 and 5), as well as CDK4 inhibitors CDKN2A/B are common. Mammary gland tumors are associated with BRCA2 underexpression due to reading frame shift and mutations in BRC repeat 3. Lastly, deletion or underexpression of p16 and PTEN and altered expression of cell-cell adhesion molecules are common factors in the development of melanoma. The genes identified were then studied to identify more key amino acid mutations that changed protein products and promoted tumorigenesis. Genes that altered expression levels of proteins were analyzed separately. Both sets of candidate genes were then analyzed with the Database for Annotation, Visualization, and Integrated Discovery (DAVID) in order to elucidate the molecular pathways involved in canine cancers and identify more genes possibly involved in tumorigenesis. The proposition of this review is that treatments for both canine and human cancers would be enhanced by comparative genomic studies.