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Review
. 2018 Sep 14;20(11):86.
doi: 10.1007/s11912-018-0733-7.

Molecular Pathways in Melanomagenesis: What We Learned from Next-Generation Sequencing Approaches

Giuseppe Palmieri  1 , Maria Colombino  2 , Milena Casula  2 , Antonella Manca  2 , Mario Mandalà  3 , Antonio Cossu  4 ; Italian Melanoma Intergroup (IMI)
Affiliations
Review

Molecular Pathways in Melanomagenesis: What We Learned from Next-Generation Sequencing Approaches

Giuseppe Palmieri et al. Curr Oncol Rep. .

Abstract

Purpose of review: Conventional clinico-pathological features in melanoma patients should be integrated with new molecular diagnostic, predictive, and prognostic factors coming from the expanding genomic profiles. Cutaneous melanoma (CM), even differing in biological behavior according to sun-exposure levels on the skin areas where it arises, is molecularly heterogeneous. The next-generation sequencing (NGS) approaches are providing data on mutation landscapes in driver genes that may account for distinct pathogenetic mechanisms and pathways. The purpose was to group and classify all somatic driver mutations observed in the main NGS-based studies.

Recent findings: Whole exome and whole genome sequencing approaches have provided data on spectrum and distribution of genetic and genomic alterations as well as allowed to discover new cancer genes underlying CM pathogenesis. After evaluating the mutational status in a cohort of 686 CM cases from the most representative NGS studies, three molecular CM subtypes were proposed: BRAFmut, RASmut, and non-BRAFmut/non-RASmut.

Keywords: Cutaneous melanoma; Genetics; Melanoma subtypes; Mutation status; Next-generation sequencing; Single-nucleotide (SNV) and copy number (CNV) variations; UV signature.

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Conflict of interest statement

Conflict of Interest

Giuseppe Palmieri, Maria Colombino, Milena Casula, Antonella Manca, Mario Mandalà, and Antonio Cossu declare they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Figures

Fig. 1
Fig. 1
Signal transduction pathways involved in melanomagenesis. Genes are evidenced according to the prevalence of alterations, including SNVs and CNVs, in the series of 686 CM samples: in red, ≥ 20% of cases; in orange, ≥ 10 to < 20%; in yellow, ≥ 5 to < 10%; in green, ≥ 2 to < 5%
Fig. 2
Fig. 2
Gene mutation frequencies in the 340 cases with the BRAFmut subtype. In red, copy number variations; in blue, pathogenetic mutations; in green, lack of additional genetic alterations. ampl, amplification; del, deletion
Fig. 3
Fig. 3
Gene mutation frequencies in the 194 cases with the RASmut subtype. In red, copy number variations; in blue, pathogenetic mutations; in green, lack of additional genetic alterations. ampl, amplification; del, deletion
Fig. 4
Fig. 4
Gene mutation frequencies in the 152 cases with the non-BRAFmut/non-RASmut subtype. In red, copy number variations; in blue, pathogenetic mutations; in green, lack of genetic alterations. ampl, amplification; del, deletion
See this image and copyright information in PMC

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