Dog melanomas share numerous similarities with human melanoma subtypes, particularly with mucosal, digital and nail locations, which show highly aggressive behavior and rapid growth in both species. The onset and neoplastic progression are accompanied by the accumulation of different molecular modifications affecting the somatic cells; these mutations can be recognized by the immune system, which is therefore able to recognize and fight cancer cells. Several studies have identified common genetic mutations between canine and human melanoma, suggesting pathogenetic pathways and common therapeutic targets. Proteoglycan-4 chondroitin sulfate (CSPG4), also known as high molecular weight-melanoma associated antigen (HMW-MAA), is implicated in numerous aspects of melanoma biology and has been identified as a target for immunotherapy in human studies and veterinarian, with encouraging results. In humans, advanced technologies, such as the Cell Search platform and Next Generation Sequencing (NGS) techniques, allow the detection of circulating melanoma cells (CMC) in peripheral blood with a high degree of sensitivity and reproducibility, allowing to monitor the spread of the disease metastatic and treatment efficacy in clinical trials. As previously reported for other malignancies, the Cell Search platform can also be used in dogs, thanks to the cross-reactivity of the antibodies against CD146 and HMW-MAA, used for the detection of CMCs. The application of Next Generation Sequencing (NGS) techniques to this area of research makes it possible to profile a large number of genomic alterations in a short time and at reasonable costs, allowing in a short time to realize personalized medicine in human oncology. The aim of the project is to characterize the oral melanoma of the dog at a cellular and molecular level in order to:

• identify and quantify the CMC to assess the prognostic potential;
• characterize the genomic alterations of the primary tumor, of the CMCs and of the circulating DNA by identifying the molecular targets of drugs;
• monitor the minimum residual disease, the action of therapy and relapses in patients. The study, thanks to the molecular characterization of the primary tumor and the circulating compartment, will contribute to increase knowledge on the biology of oral canine melanoma, in order to improve the understanding of the pathogenesis of the disease and identify potential prognostic biomarkers and therapeutic targets. Furthermore, this clinical study represents an excellent spontaneous model for some subtypes of human melanoma, comparing their progression, genetic structure and therapeutic response, in an immunocompetent subject.

• N. identificativo progetto: IZS VE 14/19 RC

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• Prof. Marina Martano, Università degli Studi di Parma
• Prof. Cristina Lecchi, Università degli Studi di Milano
• Prof. Rita Zamarchi, Università degli Studi di Padova
• Dr. Paola Modesto, Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle d'Aosta
• Dr. Elena Bozzetta, IZS PLV - SS Laboratorio Istopatologia (CEROVEC)
• Dr. Marta Vascellari, IZSVE
• Dr. Katia Capello, IZSVE