Array Comparative Genomic Hybridization analysis in Canine Acral Melanoma

Melanomas are malignant neoplasms developing from melanocytes that have been described in human beings and in several animal species, including dogs. Due to its clinical aggressiveness and tendency to metastases, human melanoma (HM) is a leading cause of skin cancer mortality in people. In dogs, it accounts for 4% of all tumors and, as in humans, it carries a bad prognosis. Both genetic and environmental factors are involved in its development. Although most of HMs are caused by UV exposure, others can arise from sun shielded locations such as the eye, digits and mucosa. Therefore, based on their location, HMs can be differentiated into melanomas of sun-exposed sites and sun-shielded sites. Melanomas of sun-exposed locations are classed as either chronically sun damaged (CSD) or non-CSD, while mucosal and acral melanomas belong to the sun-shielded category. The thesis project focuses on Canine Acral Melanoma (CAM), a malignant tumor that arises on the glabrous skin of the palms, soles and nail apparatus (subungual). The aim of the study is to deepen the whole-genome landscape in order to better understand pathogenetic pathways of CAM. To achieve this goal, we used a molecular technique called Array Comparative Genomic Hybridization (aCGH) that enabled a genome-wide analysis of all the tumor’s aberrations. Amplifications and deletions of DNA sequences were then analysed using an open-source software which allows to gain new insights and perspectives on tumors, discovering enriched biological pathways that would otherwise go unnoticed if only single aberrations, and associated genes, were characterized. The obtained results have been compared to the most recent findings in human medicine to verify if CAM is a spontaneous useful model of human counterpart. The hypothesis of using canine melanomas as a model comes from the observation that both tumors develop in presence of an intact immune system, are characterized by tumor growth over a protracted period and include inter-individual and intratumoral heterogeneity, metastasis, cancer recurrence and therapy resistance. Furthermore, dogs and humans share similar environments and, as a consequence, environmental factors that can contribute to tumor development. Finally, dogs have shorter lifespan which allows for earlier assessments of the impacts of the disease progression and overall survival.