The Molecular Landscape of Primary Acral Melanoma: A Multicenter Study of the Italian Melanoma Intergroup (IMI)

• Published in: International journal of molecular sciences 2021-04, Vol.22 (8), p.3826
• Main Authors: Elefanti, Lisa, Zamuner, Carolina, Del Fiore, Paolo, Stagni, Camilla, Pellegrini, Stefania, Dall'Olmo, Luigi, Fabozzi, Alessio, Senetta, Rebecca, Ribero, Simone, Salmaso, Roberto, Mocellin, Simone, Bassetto, Franco, Cavallin, Francesco, Tosi, Anna Lisa, Galuppini, Francesca, Dei Tos, Angelo Paolo, Menin, Chiara, Cappellesso, Rocco
• Format: Article
• Language: English
• Subjects: acral melanoma; Aged; Aged, 80 and over; ARID1A; Biomarkers, Tumor; BRAF; Chromosome 6; Chromosome rearrangements; Chromosomes; Classification; Copy number; Disease Susceptibility; DNA Copy Number Variations; Female; Genes; Genomes; Humans; Italy; Male; Medical prognosis; Melanoma; Melanoma - diagnosis; Melanoma - etiology; Melanoma - mortality; Melanoma, Cutaneous Malignant; Metastasis; Middle Aged; Mutation; Neoplasm Grading; Neoplasm Staging; Next-generation sequencing; NRAS; Nucleotides; p53 Protein; Pathogenesis; Polymorphism; Polymorphism, Single Nucleotide; PREX2; Prognosis; PTEN protein; Rac1 protein; Single-nucleotide polymorphism; Skin cancer; Skin Neoplasms - diagnosis; Skin Neoplasms - etiology; Skin Neoplasms - mortality; Ultraviolet radiation
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22083826

Acral melanoma (AM) is a rare and aggressive subtype of melanoma affecting the palms, soles, and nail apparatus with similar incidence among different ethnicities. AM is unrelated to ultraviolet radiation and has a low mutation burden but frequent chromosomal rearrangements and gene amplifications. Next generation sequencing of 33 genes and somatic copy number variation (CNV) analysis with genome-wide single nucleotide polymorphism arrays were performed in order to molecularly characterize 48 primary AMs of Italian patients in association with clinicopathological and prognostic features. was the most commonly mutated gene, followed by and , whereas promoter, , and were less frequently mutated. Gains and losses were recurrently found in the 1q, 6p, 7, 8q, 20 and 22 chromosomes involving , , , , , , and genes, and in the 6q, 9, 10, 11q and 16q chromosomes including , , and genes, respectively. This study confirmed the variety of gene mutations and the high load of CNV in primary AM. Some genomic alterations were associated with histologic prognostic features. mutations, found with a higher rate than previously reported, correlated with a low Breslow thickness, low mitotic count, low CNV of the AMs, and with early-stage of disease.