This research project is a collaboration between the CNRS of Rennes, Drs. Patrick Devauchelle (Micen-Vet) and Jérome Abadie (Veterinary School of Nantes, ONIRIS), the French Association of Swiss Mountain Dogs as well as American research teams: Drs E.Ostrander (NIH, Bethesda) and M.Breen (NCSU, Raleigh).
Histiocytic sarcoma is a tumor affecting histiocytes, cells responsible for immune functions. This disease is rare in dogs. However, certain breeds show a strong predisposition : Bernese Mountain Dog (affecting approximately 20% of dogs), Rottweiler, Golden Retriever and Flat Coated Retriever. Histiocytic sarcoma, diagnosed in Bernese Mountain Dogs and Rottweiler, is generally characterized by the development of tumors spread throughout in several organs (spleen, lungs, liver, lymphatic nodes, etc.). Conversely, in the Flat Coated Retriever, the most commonly encountered type is localized in only one organ (mainly the joints or the skin).
There are no specific symptoms aside from weight loss, fatigue and anorexia, and occasionally fever, cough and pale mucous membranes are also seen. The diagnosis to confirm their presence is done through the detection of masses and their histological or cytological analyses. The average age of detection is 6 and a half years of age, but many younger and older dogs can also be affected. No sexual predisposition has been observed.
For more information regarding the symptoms of this disease, please consult the following articles in which we have analyzed a hundred cases of histiocytic sarcomas in French dogs:
- André C, Abadie J, Hédan B, De Brito C, Lagadic M, Poujade A and Devauchelle P. Canine Proliférations histiocytaires canines : études épidémiologique, clinique et génétique de 100 cas de sarcomes histiocytaires chez le Bouvier Bernois. PMAC 2010 : Vol 45, 9-17.
- Abadie J, Hédan B, Cadieu E, De Brito C, Devauchelle P, Bourgain C et al., Epidemiology, Pathology and Genetics of Histiocytic sarcoma in the Bernese Mountain dog breed. J. Hered 2009 ; 100, Suppl. 1:19 – 27
The strong breed predisposition of this illness puts forth the genetic characteristic of the disease. For over 15 years, the CNRS at Rennes has been conducting a genetic study in collaboration with the French Swiss Bouvier club, and more recently with the Italian, Swiss, Spanish and Belgian clubs… This research has allowed us to collect a number of blood and tumoral samples on affected Bernese Mountain Dogs, as well as healthy dogs. Thanks to the analysis of a large genealogical tree of over 300 dogs, including 150 affected dogs, and to the follow-up of dogs having developed this type of cancer, we have been able to epidemiologically characterize the clinical signs and to suggest that this disease has an oligogenic mode of transmission, where only a small number of genes are implicated (Abadie et al., J. Hered. 2009; André et coll. PMCAC, 2009). As in human cancers, these so-called “predisposition” genes are necessary but may not be sufficient: certain other genes as well as environmental factors also intervene to modulate the severity and/or the age of onset (ongoing study).
To search for the genetic basis of this disease, we collect blood samples from affected dogs, including those belonging to predisposed breeds (Bernese Mountain Dog, Rottweiler, Golden Retriever, Flat Coated Retriever) to extract their DNA. The goal is to compare the genomes (all 38 chromosomes + XY) of a large number of affected and healthy dogs within the same breed, in order to identify the chromosomal regions containing the genes involved in histiocytic sarcoma, as well as the causal mutations.
To date, thanks to the thousands of blood and tumor samples collected at the Rennes laboratory, we have been able to identify several chromosomal regions that presumably contain genes involved in the development of this type of cancer (Shearin et al. Cancer Epidemiol Biomarkers Prev 2012). The following step in our research is to identify these genes and develop tests which would determine the risk that dog has to develop this type of cancer. This requires a very large number of samples. Samples of healthy dogs are the most difficult to obtain; that is why, if you have an elderly dog (> 8 years of age), his participation in this research through the submission of a blood sample (5 ml in an EDTA tube) is very important.
If your dog has a suspicion of cancer, and you want to participate in this research, it is important to contact us quickly so that we can send the sampling kits to your attending veterinarian.
Finally, like any dog, Bernese Mountain Dogs, Rottweilers and Retrievers can develop other cancers whose aggression and prognosis are variable. This is why the histological or cytological diagnosis of the identified masses is indispensable. If your dog is affected by another cancer (mastocytoma, lymphoma, melanoma …), his participation in this research is also very important. Indeed, for these cancers also encountered in other dog breeds, studies are being conducted to determine whether there is a link between these different cancers and histiocytic sarcoma.
In human medicine, this research is important to better understand the function of genes involved in the development and progression of such aggressive tumors. Indeed, given the low incidence of this cancer in humans, few genetic data are available. Therefore, dogs represent a unique spontaneous model to study the pathophysiology and genetic causes of diseases.
Other bibliographical references:
- Malivier X, Lagadic M . Histiocytic disorders, the veterinary point 2003 ; 241.
- Warmon J. The diagnosis of malignant histiocytosis is dark. Veterinary Week 2008. n°1298.
- Serre F. Lymphoma and histiocytic sarcoma in a Bernese Mountain Dog, Veterinary Point, 2009 ; N° 301 :1 – 5.
If you wish to participate in this research, please send us for any animal (affected or non affected) :
- A blood sample on EDTA tube : CNRS_Sarcome histiocytaire_Protocole
- A completed clinical questionnaire with sample authorization: CNRS_Sarcome histiocytaire_Questionnaire
- A photocopy of the dog’s pedigree une copie du pedigree du chien (if possible and if available)
We remind you that the data collected at the CNRS are confidential.
For more information, you can contact the team by phone at 02 23 23 45 09 or by email cani-dna@univ-rennes1.fr.
