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Naturally occurring melanomas in dogs as models for non‐ UV pathways of human melanomas
Author(s) -
Gillard Marc,
Cadieu Edouard,
De Brito Clotilde,
Abadie Jérôme,
Vergier Béatrice,
Devauchelle Patrick,
Degorce Frédérique,
Dréano Stephane,
Primot Aline,
Dorso Laetitia,
Lagadic Marie,
Galibert Francis,
Hédan Benoit,
Galibert MarieDominique,
André Catherine
Publication year - 2014
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/pcmr.12170
Subject(s) - melanoma , neuroblastoma ras viral oncogene homolog , pten , pathology , medicine , somatic cell , mucosal melanoma , biology , gene , cancer research , dermatology , mutation , genetics , kras , signal transduction , pi3k/akt/mtor pathway
Summary 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.