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Title: Molecular genomic profiling of melanocytic nevi.
Austin Authors: Colebatch, Andrew J;Ferguson, Peter;Newell, Felicity;Kazakoff, Stephen H;Witkowski, Tom ;Dobrovic, Alexander ;Johansson, Peter A;Saw, Robyn Pm;Stretch, Jonathan R;McArthur, Grant A;Long, Georgina V;Thompson, John F;Pearson, John V;Mann, Graham J;Hayward, Nicholas K;Waddell, Nicola;Scolyer, Richard A;Wilmott, James S
Affiliation: Royal North Shore Hospital, Sydney, NSW..
Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC, Australia
Centre for Cancer Research, Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW, Australia
QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
Melanoma Institute Australia, The University of Sydney, NSW, Australia
Tissue Pathology & Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia
School of Cancer Medicine and Molecular Cancer Prevention Program, La Trobe University, Bundoora, Victoria, Australia
Department of Clinical Pathology, University of Melbourne, Parkville, Victoria, Australia
Sydney Medical School, The University of Sydney, Sydney, NSW, Australia
Department of Melanoma and Surgical Oncology, Discipline of Surgery, Royal Prince Alfred Hospital, Sydney, NSW Australia
Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia
Issue Date: 14-Feb-2019
Date: 2019-02-14
Publication information: The Journal of investigative dermatology 2019; online first: 14 February
Abstract: The benign melanocytic nevus is the commonest tumor in humans and rarely transforms into cutaneous melanoma. Elucidation of the nevus genome is required to better understand the molecular steps of progression to melanoma. We performed whole genome sequencing on a series of 14 benign melanocytic nevi, consisting of both congenital and acquired types. All nevi had driver mutations in the MAPK signalling pathway, either BRAF V600E or NRAS Q61R/L. No additional definite driver mutations were identified. Somatic mutations in nevi with higher mutation loads showed a predominance of mutational signatures 7a and 7b, consistent with ultraviolet radiation exposure, whereas nevi with lower mutation loads (including all three congenital nevi) had a predominance of the ubiquitous signatures 1 and 5. Two nevi had mutations in promoter regions predicted to bind ETS-family transcription factors as well as subclonal mutations in the TERT promoter. This paper presents whole genome data from melanocytic nevi. We confirm that ultraviolet radiation is involved in the etiology of a subset of nevi. This study also establishes that TERT promoter mutations are present in morphologically benign skin nevi in subclonal populations, which has implications regarding the interpretation of this emerging biomarker in sensitive assays.
DOI: 10.1016/j.jid.2018.12.033
Journal: The Journal of investigative dermatology
PubMed URL: 30772300
Type: Journal Article
Subjects: Genome
melanocytic nevi
whole genome sequencing
Appears in Collections:Journal articles

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