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. 2021 Mar 5:7:555630.
doi: 10.3389/fmolb.2020.555630. eCollection 2020.

The Genetic Germline Background of Single and Multiple Primary Melanomas

Simona De Summa  1 , Antonia Lasorella  1 , Sabino Strippoli  2 , Giuseppe Giudice  3 , Gabriella Guida  4 , Rossella Elia  3 , Eleonora Nacchiero  3 , Amalia Azzariti  5 , Nicola Silvestris  6   7 , Michele Guida  2 , Stefania Guida  8 , Stefania Tommasi  1 , Rosamaria Pinto  1
Affiliations

The Genetic Germline Background of Single and Multiple Primary Melanomas

Simona De Summa et al. Front Mol Biosci. .

Abstract

Background: Melanoma has a complex molecular background and multiple genes are involved in its development and progression. The advent of next generation sequencing platforms has enabled the evaluation of multiple genes at a time, thus unraveling new insights into the genetics of melanoma. We investigated a set of germline mutations able to discriminate the development of multiple primary melanomas (MPM) vs. single site primary melanomas (SPM) using a targeted next generation sequencing panel. Materials and Methods: A total of 39 patients, 20 with SPM and 19 with MPM, were enrolled in our study. Next generation analysis was carried out using a custom targeted sequencing panel that included 32 genes known to have a role in several carcinogenic pathways, such as those involved in DNA repair, pigmentation, regulation of kinases, cell cycle control and senescence. Results: We found a significant correlation between PIK3CA:p.I391M and MPMs, compared to SPMs, p = 0.031 and a trend for the association between CYP1B1: p.N453S and SPMs, compared to MPMs (p = 0.096). We also found that both subgroups shared a spectrum of 9 alterations in 8 genes (CYP1B1: p.N453S, BAP1: p.C39fs, PIK3CA: p.I391M, CDKAL1: c.1226_1227TG, POLE: p.V1161fs, OCA2: p.R419Q, OCA2: p.R305W, MC1R: p.V60L, MGMT: p.L115F), which suggested that these genes may play a role in melanoma development. Conclusions: In conclusion, despite the small cohort of patients, we found that germline mutations, such as those of PIK3CAand CYP1B1, might contribute to the differential development of SPM and MPM.

Keywords: genetics; germline mutations; multiple primary melanomas; single primary melanoma; targeted next generation sequencing.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Oncoprint showing alterations in the 13 genes in both patient groups MPM (Blue) and SPM (red). The frequency of each gene alteration in the overall series is reported on the right. The alterations have been reported as non-synonymous SNP (blue), frameshift (green), and non-frameshift (pink) indels. Patients are indicated in the upper line.
Figure 2
Figure 2
Frequencies of alterations detected in our cohort (red column) and in ExAC/1000 Genomes (blue column) databases (*p < 0.05).
Figure 3
Figure 3
Network built with the GeneMANIA online tool displaying interactions among genes that we found to be mutated. All genes but POLE are connected by co-expression.
Figure 4A
Figure 4A
gProfiler network showing the most enriched terms for the entire custom gene panel designed for the present study.
Figure 4B
Figure 4B
The eight genes found to be mutated in the cohort.
See this image and copyright information in PMC

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