THE APPLICATION OF ARRAY COMPARATIVE GENOMIC HYBRIDIZATION IN ARCHIVAL CANINE ORAL MELANOMA REVEALS SIGNIFICANTLY ENRICHED PATHWAYS

Introduction: Human mucosal melanoma (HMM), a distinct biological entity from cutaneous melanoma, frequently harbours chromosomal rearrangement instead of somatic mutations, and is an aggressive neoplasm with severe prognosis in both man and dogs. Canine oral melanoma (COM) is currently considered a powerful model for HMM. To investigate chromosomal copy number aberrations (CNAs) in COM, array comparative genomic hybridization (aCGH) was applied to archival tissue material. Materials and Methods: Forty formalin-fixed and paraffin wax-embedded samples of treatment-naïve COM were selected from three European archives, with the presence of healthy tissue in the specimen a minimum inclusion criteria. DNA was extracted in parallel from tumour and healthy fractions and 19 specimens were subjected successfully to labelling and competitive hybridization. Data were analysed statistically through GISTIC2.0 and a pathway-enrichment analysis was performed with ClueGO. Results: Chromosomal gains and losses were confirmed to be a preponderant feature of COMs, with a particular sigmoidal trend for aberration in CFA 30 and 10. We confirmed some CNAs recently reported and described new unreported chromosomal rearrangements. Many aberrant regions overlapped with HMM-associated CNAs. Statistical analyses revealed imbalances of MAPK- and PI3K-related genes, and the perturbation of cancer-related biological processes, in particular neoangiogenetic pathways. Conclusions: Our data provide a new insight into COM biology with detection of genes and pathways related to angiogenesis, cell proliferation and immune response. Neovascularisation, described in other human melanomas, is essential for primary tumour and metastasis survival, revealing this to be a promising target for future studies aimed to deepen understanding of the pathogenesis of COM.