Genomic Characterization of Dysplastic Nevi Unveils Implications for Diagnosis of Melanoma.

Autor:	Melamed RD; Department of Systems Biology and Department of Biomedical Informatics, Columbia University, New York, New York, USA; Institute for Genomics and Systems Biology, University of Chicago, Chicago, Illinois, USA., Aydin IT; Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Rajan GS; Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Phelps R; Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Silvers DN; Department of Dermatology, Columbia University, New York, New York, USA., Emmett KJ; Department of Systems Biology and Department of Biomedical Informatics, Columbia University, New York, New York, USA., Brunner G; Department of Cancer Research, Skin Cancer Center Hornheide, Munster, Germany., Rabadan R; Department of Systems Biology and Department of Biomedical Informatics, Columbia University, New York, New York, USA. Electronic address: rr2579@cumc.columbia.edu., Celebi JT; Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York, USA. Electronic address: julide.celebi@mountsinai.org.
Jazyk:	angličtina
Zdroj:	The Journal of investigative dermatology [J Invest Dermatol] 2017 Apr; Vol. 137 (4), pp. 905-909. Date of Electronic Publication: 2016 Nov 24.
DOI:	10.1016/j.jid.2016.11.017
Abstrakt:	A well-defined risk factor and precursor for cutaneous melanoma is the dysplastic nevus. These benign tumors represent clonal hyperproliferation of melanocytes that are in a senescent-like state, but with occasional malignant transformation events. To portray the mutational repertoire of dysplastic nevi in patients with the dysplastic nevus syndrome and to determine the discriminatory profiles of melanocytic nevi (including dysplastic nevi) from melanoma, we sequenced exomes of melanocytic nevi including dysplastic nevi (n = 19), followed by a targeted gene panel (785 genes) characterization of melanocytic nevi (n = 46) and primary melanomas (n = 42). Exome sequencing revealed that dysplastic nevi harbored a substantially lower mutational load than melanomas (21 protein-changing mutations versus >100). Known "driver" mutations in genes for melanoma, including CDKN2A, TP53, NF1, RAC1, and PTEN, were not found among any melanocytic nevi sequenced. Additionally, melanocytic nevi including dysplastic nevi showed a significantly lower frequency and a different UV-associated mutational signature. These results show that although melanocytic nevi and dysplastic nevi harbor stable genomes with relatively few alterations, progression into melanomas requires additional mutational processes affecting key tumor suppressors. This study identifies molecular parameters that could be useful for diagnostic platforms. (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu