Genome sequencing of mucosal melanomas reveals that they are driven by distinct mechanisms from cutaneous melanoma

J Pathol. 2013 Jul;230(3):261-9. doi: 10.1002/path.4204.


Mucosal melanoma displays distinct clinical and epidemiological features compared to cutaneous melanoma. Here we used whole genome and whole exome sequencing to characterize the somatic alterations and mutation spectra in the genomes of ten mucosal melanomas. We observed somatic mutation rates that are considerably lower than occur in sun-exposed cutaneous melanoma, but comparable to the rates seen in cancers not associated with exposure to known mutagens. In particular, the mutation signatures are not indicative of ultraviolet light- or tobacco smoke-induced DNA damage. Genes previously reported as mutated in other cancers were also mutated in mucosal melanoma. Notably, there were substantially more copy number and structural variations in mucosal melanoma than have been reported in cutaneous melanoma. Thus, mucosal and cutaneous melanomas are distinct diseases with discrete genetic features. Our data suggest that different mechanisms underlie the genesis of these diseases and that structural variations play a more important role in mucosal than in cutaneous melanomagenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • DNA Copy Number Variations
  • DNA, Neoplasm / chemistry
  • DNA, Neoplasm / genetics
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / pathology
  • Exome
  • Female
  • Genital Neoplasms, Female / genetics*
  • Genital Neoplasms, Female / pathology
  • Genital Neoplasms, Male / genetics*
  • Genital Neoplasms, Male / pathology
  • Genomics
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Male
  • Melanoma / genetics*
  • Melanoma / pathology
  • Molecular Sequence Data
  • Mucous Membrane / pathology
  • Mutation
  • Mutation Rate
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / pathology
  • Paranasal Sinus Neoplasms / genetics*
  • Paranasal Sinus Neoplasms / pathology
  • Polymorphism, Single Nucleotide
  • Proto-Oncogene Proteins B-raf / genetics
  • Rectal Neoplasms / genetics*
  • Rectal Neoplasms / pathology
  • Sequence Analysis, DNA
  • Sequence Analysis, RNA
  • Skin Neoplasms / genetics
  • Skin Neoplasms / pathology
  • Skin Neoplasms / secondary


  • DNA, Neoplasm
  • Proto-Oncogene Proteins B-raf