Mutational signatures and chromosome alteration profiles of squamous cell carcinomas of the vulva

Exp Mol Med. 2018 Feb 9;50(2):e442. doi: 10.1038/emm.2017.265.


Vulvar squamous cell carcinoma (SCC) consists of two different etiologic categories: human papilloma virus (HPV)-associated (HPV (+)) and HPV-non-associated (HPV (-)). There have been no genome-wide studies on the genetic alterations of vulvar SCCs or on the differences between HPV (+) and HPV (-) vulvar SCCs. In this study, we performed whole-exome sequencing and copy number profiling of 6 HPV (+) and 9 HPV (-) vulvar SCCs and found known mutations (TP53, CDKN2A and HRAS) and copy number alterations (CNAs) (7p and 8q gains and 2q loss) in HPV (-) SCCs. In HPV (+), we found novel mutations in PIK3CA, BRCA2 and FBXW7 that had not been reported in vulvar SCCs. HPV (-) SCCs exhibited more mutational loads (numbers of nonsilent mutations and driver mutations) than HPV (+) SCCs, but the CNA loads and mutation signatures between HPV (+) and HPV (-) SCCs did not differ. Of note, 40% and 40% of the 15 vulvar SCCs harbored PIK3CA and FAT1 alterations, respectively. In addition, we found that the SCCs harbored kataegis (a localized hypermutation) in 2 HPV (+) SCCs and copy-neutral losses of heterozygosity in 4 (one HPV (+) and 3 HPV (-)) SCCs. Our data indicate that HPV (+) and HPV (-) vulvar SCCs may have different mutation and CNA profiles but that there are genomic features common to SCCs. Our data provide useful information for both HPV (+) and HPV (-) vulvar SCCs and may aid in the development of clinical treatment strategies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles
  • Biomarkers, Tumor
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / virology
  • Chromosome Aberrations*
  • Chromosome Mapping
  • DNA Copy Number Variations
  • DNA Mutational Analysis
  • Exome Sequencing
  • Female
  • Gene Expression Profiling
  • Genetic Predisposition to Disease
  • Humans
  • Loss of Heterozygosity
  • Middle Aged
  • Mutation*
  • Neoplasm Staging
  • Tumor Burden
  • Vulvar Neoplasms / genetics*
  • Vulvar Neoplasms / pathology
  • Vulvar Neoplasms / virology


  • Biomarkers, Tumor