title: The extent of whole-genome copy number alterations predicts aggressive features in primary melanomas.
abstract: Recent evidence indicates that melanoma comprises distinct types of tumors and suggests that specific morphological features may help predict its clinical behavior. Using a SNP-array approach, we quantified chromosomal copy number alterations (CNA) across the whole genome in 41 primary melanomas and found a high degree of heterogeneity in their genomic asset. Association analysis correlating the number and relative length of CNA with clinical, morphological, and dermoscopic attributes of melanoma revealed that features of aggressiveness were strongly linked to the overall amount of genomic damage. Furthermore, we observed that melanoma progression and survival were mainly affected by a low number of large chromosome losses and a high number of small gains. We identified the alterations most frequently associated with aggressive melanoma, and by integrating our data with publicly available gene expression profiles, we identified five genes which expression was found to be necessary for melanoma cells proliferation. In conclusion, this work provides new evidence that the phenotypic heterogeneity of melanoma reflects a parallel genetic diversity and lays the basis to define novel strategies for a more precise prognostic stratification of patients.
authors.affiliation: Laboratory of Translational Research, Arcispedale S. Maria Nuova-IRCCS, Reggio Emilia, Italy.
authors.forename: Greta
authors.initials: G
authors.lastname: Gandolfi
authors.affiliation: Skin Cancer Unit, Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Longo
authors.affiliation: Skin Cancer Unit, Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia, Italy.
authors.forename: Elvira
authors.initials: E
authors.lastname: Moscarella
authors.affiliation: Department of Dermatology and Venerology, Non-Melanoma Skin Cancer Unit, Medical University of Graz, Graz, Austria.
authors.forename: Iris
authors.initials: I
authors.lastname: Zalaudek
authors.affiliation: Laboratory of Translational Research, Arcispedale S. Maria Nuova-IRCCS, Reggio Emilia, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Sancisi
authors.affiliation: Skin Cancer Unit, Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia, Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Raucci
authors.affiliation: Laboratory of Translational Research, Arcispedale S. Maria Nuova-IRCCS, Reggio Emilia, Italy.
authors.forename: Gloria
authors.initials: G
authors.lastname: Manzotti
authors.affiliation: Laboratory of Translational Research, Arcispedale S. Maria Nuova-IRCCS, Reggio Emilia, Italy.
authors.forename: Mila
authors.initials: M
authors.lastname: Gugnoni
authors.affiliation: Pathology Unit, Arcispedale S. Maria Nuova-IRCCS, Reggio Emilia, Italy.
authors.forename: Simonetta
authors.initials: S
authors.lastname: Piana
authors.affiliation: Skin Cancer Unit, Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia, Italy.|Dermatology Unit, Second University of Naples, Naples, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Argenziano
authors.affiliation: Laboratory of Translational Research, Arcispedale S. Maria Nuova-IRCCS, Reggio Emilia, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Ciarrocchi
mesh_terms: D000328:Adult; D049109:Cell Proliferation / Q000235:genetics*; D002869:Chromosome Aberrations; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008545:Melanoma / Q000175:diagnosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis
keywords: aggressiveness; copy number alterations; dermoscopy; primary melanoma; whole-genome SNP array