Breed-related tumours in Bernese mountain dogs and Flat-coated retrievers and the predisposition to Histiocytic Sarcoma

Abstract

The high prevalence of histiocytic sarcoma (HS), one of the most aggressive and still nearly always fatal tumours, in the Bernese mountain dog (BMD) and the Flat-coated retriever (FCR), leads to increasing concern among owners, breed societies and veterinarians worldwide. To turn the tide in this devastating disease, more insight into the disease process is urgently needed. This thesis first of all provides insight into the precise causes of death of both breeds. This shows that malignant tumours are the main reason for the relatively short life expectancy, and that 1 in 7 of all BMDs and FCRs die as a result of HS. Secondly, it also provides insight into how HS can be differentiated from other malignant tumours. With a high probability, there are also dog-equivalents of human HS-subtypes. In addition, there are partial genetic or environmental differences between breeds in the development of HS. Thirdly, this thesis gives, for the first time, a complete overview of the full scope of all possible clinical presentations of HS in the BMD and FCR. It is notable, among other things, that the localized HS-disseminated HS (LHS-DHS)-distributions are exactly reversed in the BMD (more DHS) and FCR (more LHS). Also, this thesis describes the first clinical study of safety and efficacy of artesunate. Artesunate is able to affect the growth of spontaneously occurring, inoperable tumours, including HS, in dogs. Further, this thesis demonstrates that the BMD is an attractive model for studies of the genetics of HS. The very first genome-wide association studies (GWAS) of HS reveal a number of genetic changes, present in 96% of all BMDs with HS, which may have a major contribution to susceptibility to HS. Finally, an analysis is presented of all currently known genetic variants in dogs and humans with HS, together with their possible mutation-targeted therapies, their efficacy and a contemplation on the future. This shows that the BMD and FCR with HS can both function as animal model for human HS. With a joint effort, a major acceleration of knowledge is expected that can improve the survival rate of this devastating disease in humans and animals.