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Journal of Heredity Advance Access published online on June 16, 2009
Journal of Heredity, doi:10.1093/jhered/esp039
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© The American Genetic Association. 2009. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org.

Epidemiology, Pathology, and Genetics of Histiocytic Sarcoma in the Bernese Mountain Dog Breed

Jérôme Abadie*, Benoit Hédan*, Edouard Cadieu, Clotilde De Brito, Patrick Devauchelle, Catherine Bourgain, Heidi G. Parker, Amaury Vaysse, Patricia Margaritte-Jeannin, Francis Galibert, Elaine A. Ostrander, and Catherine André

Unité d'Anatomie pathologique, Ecole Nationale Vétérinaire de Nantes, BP40706, 44307 Nantes cedex 3, France (Abadie); Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, 50 South Drive, Bethesda, MD (Cadieu, Parker, and Ostrander); Institut de Génétique et Développement, Une unité mixte de recherche 6061 Centre national de la recherche scientifique/Université de Rennes1, Faculté de Médecine, Rennes, France (Hédan, Brito, Vaysse, Galibert, André); Centre anti-cancereux, Ecole nationale vétérinaire d’Alfort 7 avenue du general de Gaulle 94700, Maisons-Alfort, France (Devauchelle); Institut Inserm U535—Genetique Epidemiologique et Structure des Populations humaines, Hôpital Paul Brousse Bâtiment Leriche B.P., Villejuif, France (Bourgain and Margaritte-Jeannin). Benoit Hédan is now at Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC

Address correspondence to C. André at the address above, or e-mail: catherine.andre{at}univ-rennes1.fr.

Histiocytic sarcoma (HS) refers to a highly aggressive and frequently disseminated neoplastic disease belonging to the class of canine histiocytic proliferative disorders. Disseminated HS (previously called malignant histiocytosis) is highly breed specific, with Bernese mountain dogs (BMDs), rottweilers, and retrievers having a high prevalence with a frequency of approximately 25% in the BMD breed. We collected DNA samples and clinical information from 800 BMDs, of which 200 are affected by HS. To better characterize the physiopathology and epidemiology, an in-depth analysis of 89 BMD cases has been performed. The mean age of onset was 6.5 years, males and females being equally affected. The clinical features, biochemical parameters, and pathological features have been determined. The life span after diagnosis has been estimated to be 49 days. A large BMD pedigree of 327 dogs, 121 of which are affected, was assembled. Using a subset of 160 BMDs, encompassing 21 complete sibships, we now propose an oligogenic transmission mode of the disease. Whole-genome linkage scans as well as association studies using a case/control analysis, in parallel with expression profiling of neoplastic versus normal histiocytes, are all underway. Altogether, these complementary approaches are expected to localize the genes for HS in the BMD, leading to advances in our knowledge of histiocyte diseases in dogs and humans.

Key Words: Bernese mountain dogs • cancer • dog • genetics • histiocytic sarcoma

* Authors equally contributed to the work.

Corresponding Editor: Dr Marilyn Menotti-Raymond

Received November 25, 2008
Revised April 8, 2009
Accepted May 15, 2009


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