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

Lisa Elefanti,Simone Mocellin,Francesca Galuppini,Luigi Dall’Olmo,Stefania Pellegrini,Paolo Del Fiore,Anna Lisa Tosi,Alessio Fabozzi,Angelo Paolo Dei Tos,Simone Ribero,Rebecca Senetta,Rocco Cappellesso,Francesco Cavallin,Carolina Zamuner,Roberto Salmaso,Chiara Menin,Camilla Stagni,Franco Bassetto

doi:10.3390/ijms22083826

Abstract

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. BRAF was the most commonly mutated gene, followed by NRAS and TP53, whereas TERT promoter, KIT, and ARID1A were less frequently mutated. Gains and losses were recurrently found in the 1q, 6p, 7, 8q, 20 and 22 chromosomes involving PREX2, RAC1, KMT2C, BRAF, CCND1, TERT, and AKT3 genes, and in the 6q, 9, 10, 11q and 16q chromosomes including CDKN2A, PTEN, and ADAMTS18 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. BRAF 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.

Highlights

Acral melanoma (AM) is a rare subtype of malignant melanoma that originates from the glabrous skin of the palms, soles, and nail apparatus [1]
The remaining 48 patients (81%) with analyzable samples had a mean age of 71.2 ± 13.2 years and a male to female ratio of 1:1
Most AMs were located in the foot (79%), followed by nail (15%) and hand (6%)

Summary

Introduction

Acral melanoma (AM) is a rare subtype of malignant melanoma that originates from the glabrous skin of the palms, soles, and nail apparatus (subungual) [1]. Its annual incidence is similar among the different racial groups worldwide, settling at about 1 case per 100,000 people, in proportion AM is relatively rare in the European-derived population but common in Asian, African, and Hispanic people [2,3]. For this reason, most studies focused on these last ethnicities. The treatment is the same as for the other cutaneous melanomas: wide surgical removal of the primary tumor and, if feasible, of regional nodal metastases for local disease and immunotherapy or targeted therapy (more rarely chemotherapy) for metastatic disease [9]

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