Whole-genome sequencing of acral melanoma reveals genomic complexity and diversity

Felicity Newell(QIMR Berghofer Medical Research Institute), James S. Wilmott(The University of Sydney), Peter A. Johansson(QIMR Berghofer Medical Research Institute), Kátia Nones(QIMR Berghofer Medical Research Institute), Venkateswar Addala(The University of Queensland), Pamela Mukhopadhyay(QIMR Berghofer Medical Research Institute), Natasa Broit(The University of Queensland), Carol M. Amato(University of Colorado Cancer Center), Robert J. Van Gulick(University of Colorado Cancer Center), Stephen H. Kazakoff(QIMR Berghofer Medical Research Institute), Ann‐Marie Patch(QIMR Berghofer Medical Research Institute), Lambros T. Koufariotis(QIMR Berghofer Medical Research Institute), Vanessa Lakis(QIMR Berghofer Medical Research Institute), Conrad Leonard(QIMR Berghofer Medical Research Institute), Scott Wood(QIMR Berghofer Medical Research Institute), Oliver Holmes(QIMR Berghofer Medical Research Institute), Qinying Xu(QIMR Berghofer Medical Research Institute), Karl D. Lewis(University of Colorado Cancer Center), Theresa Medina(University of Colorado Cancer Center), René González(University of Colorado Cancer Center), Robyn P.M. Saw(The University of Sydney), Andrew J. Spillane(The University of Sydney), Jonathan R. Stretch(The University of Sydney), Robert V. Rawson(The University of Sydney), Peter M. Ferguson(The University of Sydney), Tristan J. Dodds(The University of Sydney), John F. Thompson(The University of Sydney), Georgina V. Long(The University of Sydney), Mitchell P. Levesque(University of Zurich), William A. Robinson(University of Colorado Cancer Center), John V. Pearson(QIMR Berghofer Medical Research Institute), Graham J. Mann(Australian National University), Richard A. Scolyer(The University of Sydney), Nicola Waddell(The University of Queensland), Nicholas K. Hayward(QIMR Berghofer Medical Research Institute)
Nature Communications
October 16, 2020
10.1038/s41467-020-18988-3
Cited by 178Open Access
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Abstract

To 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.

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