00615A: Heritable and Sporadic Genetic Lesions in Canine Lymphoma
Grant Status: Closed
It has been apparent for some time that certain dog breeds are prone to develop certain types of cancer. Specifically, studies completed between the late 1960's and the early 1980's defined relative risk of lymphoma for different dog breeds. Yet, there has been little progress since then to define factors that account for this risk. As part of ongoing programs supported by the AKC CHF in our laboratories, we showed recently that the breed-specific risk of lymphoma extends beyond the simple disease condition to a predisposition for specific forms of lymphoma. More importantly, we showed there are recurrent chromosomal abnormalities that segregate with specific forms of lymphoma and that are more common in Golden Retrievers than in other breeds, suggesting breed-specific profiles of genetic abnormalities will be found in canine lymphoma. To continue this work, we plan to use contemporary "array-based" technologies to identify genes that map to these regions and how they contribute to the disease. We anticipate that the results from this work will allow us to predict how heritable factors influence the occurrence of abnormalities in these genes, and will set the groundwork to identify specific genes associated with breed-dependent cancer risk.
Frantz, A. M., Sarver, A. L., Ito, D., Phang, T. L., Karimpour-Fard, A., Scott, M. C., … Modiano, J. F. (2013). Molecular Profiling Reveals Prognostically Significant Subtypes of Canine Lymphoma. Veterinary Pathology, 50(4), 693–703. https://doi.org/10.1177/0300985812465325
Ito, D., Endicott, M. M., Jubala, C. M., Helm, K. M., Burnett, R. C., Husbands, B. D., … Modiano, J. F. (2011). A Tumor-Related Lymphoid Progenitor Population Supports Hierarchical Tumor Organization in Canine B-Cell Lymphoma: Canine B-Cell Lymphoma. Journal of Veterinary Internal Medicine, 25(4), 890–896. https://doi.org/10.1111/j.1939-1676.2011.0756.x
Ito, Daisuke, Frantz, A. M., Williams, C., Thomas, R., Burnett, R. C., Avery, A. C., … Modiano, J. F. (2012). CD40 ligand is necessary and sufficient to support primary diffuse large B-cell lymphoma cells in culture: a tool for in vitro preclinical studies with primary B-cell malignancies. Leukemia & Lymphoma, 53(7), 1390–1398. https://doi.org/10.3109/10428194.2011.654337
Ito, Daisuke, O’Brien, T. D., & Modiano, J. F. (2010). Exclusion of cytoplasmic fragments in flow cytometric analysis of lymph node samples from dogs with lymphoma using membrane-permeable violet laser-excitable DNA-binding fluorescent dye (DyeCycle Violet). Veterinary Clinical Pathology, 39(4), 494–498. https://doi.org/10.1111/j.1939-165X.2010.00252.x
Tonomura, N., Elvers, I., Thomas, R., Megquier, K., Turner-Maier, J., Howald, C., … Lindblad-Toh, K. (2015). Genome-wide Association Study Identifies Shared Risk Loci Common to Two Malignancies in Golden Retrievers. PLOS Genetics, 11(2), e1004922. https://doi.org/10.1371/journal.pgen.1004922
Help Future Generations of Dogs
Participate in canine health research by providing samples or by enrolling in a clinical trial. Samples are needed from healthy dogs and dogs affected by specific diseases.