Naturally occurring melanomas in dogs as models for non‐UV pathways of human melanomas |
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Authors: | Marc Gillard Edouard Cadieu Clotilde De Brito Jérôme Abadie Béatrice Vergier Patrick Devauchelle Frédérique Degorce Stephane Dréano Aline Primot Laetitia Dorso Marie Lagadic Francis Galibert Benoit Hédan Marie‐Dominique Galibert Catherine André |
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Institution: | 1. CNRS, UMR 6290, Institut Génétique et Développement de Rennes, , Rennes, France;2. Faculté de Médecine, SFR Biosit, Université Rennes 1, , Rennes, France;3. Laboratoire d'Histopathologie Animale, ONIRIS, Ecole Nationale Vétérinaire, Agroalimentaire et de l'Alimentation Nantes‐Atlantique, , Nantes, France;4. LUNAM University, Oniris, AMaROC, , Nantes, France;5. Service de Pathologie, CHU Bordeaux, H?pital du Haut‐Lévêque, , Pessac, France;6. MICEN‐VET, , Creteil, France;7. Laboratoire d'Anatomie Pathologique Vétérinaire du Sud‐Ouest, , Toulouse, France;8. Laboratoire IDEXX Alfort, , Alfortville, France |
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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 4‐yr 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. |
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Keywords: | melanomas dog model epidemiology his‐tology genetics somatic mutations non‐UV pathways |
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