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

Nat Commun. 2020 Oct 16;11(1):5259. doi: 10.1038/s41467-020-18988-3.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Female
  • GTP Phosphohydrolases / genetics
  • GTP Phosphohydrolases / metabolism
  • Gene Amplification
  • Gene Dosage
  • Genomics
  • Humans
  • Male
  • Melanoma / genetics*
  • Melanoma / metabolism
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mutation
  • Oxidoreductases / genetics
  • Oxidoreductases / metabolism
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins B-raf / metabolism
  • Receptor, Notch2 / genetics
  • Receptor, Notch2 / metabolism
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / metabolism
  • Whole Genome Sequencing

Substances

  • Membrane Glycoproteins
  • Membrane Proteins
  • NOTCH2 protein, human
  • Receptor, Notch2
  • Oxidoreductases
  • TYRP1 protein, human
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • GTP Phosphohydrolases
  • NRAS protein, human