GRCh38 · COSMIC v96


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Genomic Characterization of Dysplastic Nevi Unveils Implications for Diagnosis of Melanoma.
Paper ID
Melamed RD, Aydin IT, Rajan GS, Phelps R, Silvers DN, Emmett KJ, Brunner G, Rabadan R and Celebi JT
Department of Systems Biology and Department of Biomedical Informatics, Columbia University, New York, NY, USA; Institute for Genomics and Systems Biology, University of Chicago, Chicago, IL, USA.
The Journal of investigative dermatology, 2016
ISSN: 1523-1747
PMID: 27890785 (view at PubMed or Europe PMC)
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 ultraviolet-associated mutational signature. These results show that while 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.
Paper Status