Glioma in dogs: interest of spontaneous models for the genetics of human gliomas

Presenter Maud Rimbault
Authors M. Rimbault (1), C. de Brito (1), A. Primot (1), R. Ulvé (1), M. Rault (1), N. Botherel (1), C. Escriou (2), J. Abadie (3), L. Lagoutte (1), D. Dullin (2), D. Fanuel (3), M.A. Colle (3), P. Devauchelle (4), J-L. Thibaud (4), S. Blot (5), A. Rousseau (6), J. Mosser (1), P. Menei (7), B. Hédan (1) and C. André (1)
Affiliations 1. Institut de Génétique et Développement de Rennes IGDR, UMR 6290 CNRS/Université de Rennes1, Faculté de Médecine, Rennes, France 2. Unité de Pathologie médicale des carnivores (Neurologie et troubles du comportement), VetAgro-Sup, Marcy l’Etoile, France 3. Unité AMaROC, Oniris, Atlanpole La Chantrerie, Nantes, France 4. MICEN VET, Europarc, Créteil, France 5. UPR de neurobiologie, Ecole Nationale Vétérinaire d’Alfort, Maisons Alfort, France 6. Département de Pathologie Cellulaire et Tissulaire, 
CHU d'Angers, Angers, France 7. Département de Neurochirurgie, INSERM U1066, CHU d'Angers, 
Angers, France
Presentation Type Talk


Human glioma are brain cancers with a dramatic 5 year survival time of 5% even applying the unique reference treatment based on radio- and chemotherapy. Interestingly, among the many dog breeds prone to spontaneously develop cancers, brachycephalic breeds (Boxers, Bulldogs, Boston terriers…) are particularly affected by glial tumors. Dogs share the same environment as humans and have also anatomical and physiological similarities, thus constituting a relevant model for the genetics and therapies of brain tumors.
Thanks to the national Cani-DNA biobank and its veterinary network (the 4 Veterinary Schools, Antagene, private practices and cancer centers) managed at CNRS Rennes (France), samples for 50 glioma affected and >100 control dogs, as well as 1400 brachycephalic dogs have been collected and DNA extracted and stored.
With the goal to compare dog and human gliomas in mind, we performed a retrospective study of 100 canine glioma cases, allowing a clinical, epidemiological and histological characterization of these canine tumors. The predominant localization of glioma to the frontal lobe, predisposed breeds (mainly brachycephalic dogs from the European Mastiff line) and mean age of onset were revealed by the analysis of 20 cases with imaging and 15 cases with histology. We showed that dog gliomas present surprising anatomic and clinical homologies, with comparable histopathological subtypes as in human gliomas.
These results led us to analyze 2 cases for which brain tissue had been collected. We identified a BRAF-MBP gene fusion in one case using RNAseq and we are currently checking for recurrence in the collected samples, as well as for the presence of this translocation in human glioma cases. Using affected cases and controls of the same breeds, we plan to pursue the identification of somatic alterations by transcriptome analyzes (RNAseq) and exome sequencing (WES) and to carry out genetic linkage and/or genetic association studies (GWAS) to identify genomic regions involved in predisposition. We will also search if and how the artificial selection that led to specific morphological characteristics, such as the shape of the dog’s skull (brachycephaly), would have also led to glioma predisposition.