Whole-genome sequencing of acral melanoma reveals genomic complexity and diversity
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Published:2020-10-16
Issue:1
Volume:11
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Newell FelicityORCID, Wilmott James S., Johansson Peter A., Nones Katia, Addala VenkateswarORCID, Mukhopadhyay Pamela, Broit NatasaORCID, Amato Carol M.ORCID, Van Gulick Robert, Kazakoff Stephen H.ORCID, Patch Ann-MarieORCID, Koufariotis Lambros T., Lakis Vanessa, Leonard ConradORCID, Wood ScottORCID, Holmes Oliver, Xu Qinying, Lewis Karl, Medina Theresa, Gonzalez Rene, Saw Robyn P. M.ORCID, Spillane Andrew J.ORCID, Stretch Jonathan R., Rawson Robert V., Ferguson Peter M., Dodds Tristan J., Thompson John F.ORCID, Long Georgina V.ORCID, Levesque Mitchell P., Robinson William A., Pearson John V., Mann Graham J., Scolyer Richard A.ORCID, Waddell NicolaORCID, Hayward Nicholas K.ORCID
Abstract
AbstractTo increase understanding of the genomic landscape of acral melanoma, a rare form of melanoma occurring on palms, soles or nail beds, whole genome sequencing of 87 tumors with matching transcriptome sequencing for 63 tumors was performed. Here we report that mutational signature analysis reveals a subset of tumors, mostly subungual, with an ultraviolet radiation signature. Significantly mutated genes are BRAF, NRAS, NF1, NOTCH2, PTEN and TYRP1. Mutations and amplification of KIT are also common. Structural rearrangement and copy number signatures show that whole genome duplication, aneuploidy and complex rearrangements are common. Complex rearrangements occur recurrently and are associated with amplification of TERT, CDK4, MDM2, CCND1, PAK1 and GAB2, indicating potential therapeutic options.
Funder
Department of Health | National Health and Medical Research Council Deborah and John McMurtrie MIA Pathology Fellowship Jani Haenke Melanoma Pathology Fellowship University of Sydney Medical Foundation Melanoma Institute Australia New South Wales Health Pathology Royal Prince Alfred Hospital
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry
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