[Show abstract][Hide abstract] ABSTRACT: Spontaneously occurring melanomas are frequent in dogs. They appear at the same localizations as in humans, i.e. skin, mucosal sites, nail matrix and eyes. They display variable behaviors: tumors at oral localizations are more frequent and aggressive than at other anatomical sites. Interestingly, dog melanomas are associated with strong breed predispositions and overrepresentation of black-coated dogs. Epidemiological analysis of 2350 affected dogs showed that poodles are at high risk of developing oral melanoma, while schnauzers or Beauce shepherds mostly developped cutaneous melanoma. Clinical and histopathological analyses were performed on a cohort of 153 cases with a four-year follow-up. Histopathological characterization showed that most canine tumors are intradermal and homologous to human rare morphological melanomas types -"nevocytoid type" and "animal type"-. Tumor cDNA sequencing data, obtained from 95 dogs for six genes, relevant to human melanoma classification, detected somatic mutations in oral melanoma, in NRAS and PTEN genes, at human hotspot sites, but not in BRAF. Altogether, these findings support the relevance of the dog model for comparative oncology of melanomas, especially for the elucidation of non-UV induced pathways. This article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: Canine histiocytic diseases are divided into several entities owing to their epidemiological, clinical, and pathological characteristics. This article focuses on the disseminated histiocytic sarcoma, previously termed malignant histiocytosis, for which the search of the genetic bases is ongoing in the CNRS of Rennes. We will present epidemiological, clinical, and histopathological characteristics of the condition owing to the in-depth analysis of 100 cases of histiocytic sarcoma-affected Bernese mountain dogs. The mean age of onset was 6.5 years, males and females being equally affected. The lifespan after diagnosis has been estimated to be 49 days. Moreover, we present the data obtained by the analysis of a large pedigree of more than 300 dogs for which DNA is being analyzed. We propose an oligogenic transmission mode of this cancer and show an elevated frequency of other cancer types in related dogs of the family in the Bernese mountain dog breed.
Pratique Médicale et Chirurgicale de l Animal de Compagnie 01/2010; 45(1):9-17. DOI:10.1016/j.anicom.2010.02.003
[Show abstract][Hide abstract] ABSTRACT: 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.
The Journal of heredity 07/2009; 100 Suppl 1(Supplement 1):S19-27. DOI:10.1093/jhered/esp039 · 2.09 Impact Factor