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

Felicity Newell; James S. Wilmott; Peter A. Johansson; Kátia Nones; Venkateswar Addala; Pamela Mukhopadhyay; Natasa Broit; Carol M. Amato; Robert J. Van Gulick; Stephen H. Kazakoff; Ann‐Marie Patch; Lambros T. Koufariotis; Vanessa Lakis; Conrad Leonard; Scott Wood; Oliver Holmes; Qinying Xu; Karl D. Lewis; Theresa Medina; René González; Robyn P.M. Saw; Andrew J. Spillane; Jonathan R. Stretch; Robert V. Rawson; Peter M. Ferguson; Tristan J. Dodds; John F. Thompson; Georgina V. Long; Mitchell P. Levesque; William A. Robinson; John V. Pearson; Graham J. Mann; Richard A Scolyer; Nicola Waddell; Nicholas K. Hayward

doi:10.1038/s41467-020-18988-3

Abstract

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

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Whole-genome landscape of mucosal melanoma reveals diverse drivers and therapeutic targets

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Abstract 2221: Molecular analysis finds excision margin width predictive of recurrence in acral melanoma