01410B: Positional Cloning of Histiocytic Sarcoma (HS) in the Bernese Mountain Dog (BMD) and Flat Coated Retriever (Part B - See also 01410A)
Grant Status: Closed
Project Summary
While rare in the general canine population, histiocytic cancers occur at a high rate in several breeds, most notably Bernese mountain dogs (BMD) and flat-coated retrievers (FCR). We have identified two genomic regions that associate with histiocytic cancer in the BMD and two different regions in the FCR. We propose to identify the specific DNA level mutations that increase susceptibility to histiocytic cancers in both breeds. We will determine how the two regions identified in each breed interact, and identify the changes that likely take place inside the cells that lead to cancer development. We have preliminary evidence for one locus that indicates we are likely to find mutations that affect how genes are regulated rather than changing the proteins produced by the genes. We are designing an assay to determine the function of any regulatory sequences in that region and will apply these methods to the other associated regions as well. We believe that the proposed experiments will lead to the availability of genetic testing, improved diagnostics, and development of new treatments for dogs affected with histiocytic sarcoma.
Publication(s)
Andre, C., & Passais, J. (2012). Le chien dans la pathologie et la génétique comparée: Exemples de maladies et de gènes partageés entre l’homme et le chien. Bulletin de l’Académie vétérinaire de France, (1), 215.https://doi.org/10.4267/2042/48210
Hedan, B., Thomas, R., Motsinger-Reif, A., Abadie, J., Andre, C., Cullen, J., & Breen, M. (2011). Molecular cytogenetic characterization of canine histiocytic sarcoma: A spontaneous model for human histiocytic cancer identifies deletion of tumor suppressor genes and highlights influence of genetic background on tumor behavior. BMC Cancer, 11(1). https://doi.org/10.1186/1471-2407-11-201
Shearin, A. L., Hedan, B., Cadieu, E., Erich, S. A., Schmidt, E. V., Faden, D. L., … Ostrander, E. A. (2012). The MTAP-CDKN2A Locus Confers Susceptibility to a Naturally Occurring Canine Cancer. Cancer Epidemiology Biomarkers & Prevention, 21(7), 1019–1027. https://doi.org/10.1158/1055-9965.EPI-12-0190-T
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