Whole-exome sequencing of acquired nevi identifies mechanisms for development and maintenance of benign neoplasms.

Whole-exome sequencing of acquired nevi identifies mechanisms for development and maintenance of benign neoplasms.

J Invest Dermatol. 2018 Feb 21;:

Authors: Stark MS, Tan JM, Tom L, Jagirdar K, Lambie D, Schaider H, Soyer HP, Sturm RA

Abstract
The melanoma transformation rate of each nevus is rare despite the detection of oncogenic BRAF or NRAS mutations in 100% of nevi. Acquired melanocytic nevi (AMN) do however mimic melanoma and ∼30% of all melanomas arise within pre-existing nevi. Using whole-exome sequencing of 30 matched nevi, adjacent normal skin, and saliva we sought to identify the underlying genetic mechanisms for nevus development. All nevi were clinically, dermoscopically, and histopathologically documented. In addition to identifying somatic mutations, we found mutational signatures relating to ultra-violet radiation (UVR) mirroring those found in cutaneous melanoma. In nevi we frequently observed the presence of the UVR mutation signature compared to adjacent normal skin (97% vs 10% respectively). In copy number aberration (CNA) analysis, in nevi with copy number loss of tumor suppressor genes (TSG), these were balanced by loss of potent oncogenes. Moreover, reticular and non-specific patterned nevi revealed an increased (p<0.0001) number of CNA as compared with globular nevi. The mutation signature data generated in this study confirms that UVR strongly contributes to nevogenesis. Copy number changes reflect at a genomic level the dermoscopic differences of AMN. Lastly, we propose that the balanced loss of TSGs and oncogenes is a protective mechanism of AMN.

PMID: 29476775 [PubMed - as supplied by publisher]

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