High-resolution genomic profiling of human papillomavirus-associated vulval neoplasia

K J Purdie, C A Harwood, K Gibbon, T Chaplin, B D Young, J B Cazier, N Singh, I M Leigh, C M Proby

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

BACKGROUND: The incidence of human papillomavirus-associated vulval neoplasia is increasing worldwide; yet the associated genetic changes remain poorly understood.

METHODS: We have used single-nucleotide polymorphism microarray analysis to perform the first high-resolution investigation of genome-wide allelic imbalance in vulval neoplasia. Our sample series comprised 21 high-grade vulval intraepithelial neoplasia and 6 vulval squamous cell carcinomas, with paired non-lesional samples used to adjust for normal copy number variation.

RESULTS: Overall the most common recurrent aberrations were gains at 1p and 20, with the most frequent deletions observed at 2q, 3p and 10. Copy-neutral loss of heterozygosity at 6p was a recurrent event in vulval intraepithelial neoplasia. The pattern of genetic alterations differed from the characteristic changes we previously identified in cutaneous squamous cell carcinomas. Vulval neoplasia samples did not exhibit gain at 5p, a frequent recurrent aberration in a series of cervical tumours analysed elsewhere using an identical protocol.

CONCLUSION: This series of 27 vulval samples comprises the largest systematic genome-wide analysis of vulval neoplasia performed to date. Despite shared papillomavirus status and regional proximity, our data suggest that the frequency of certain genetic alterations may differ in vulval and cervical tumours.

Original languageEnglish
Pages (from-to)1044-51
Number of pages8
JournalBritish Journal of Cancer
Volume102
Issue number6
DOIs
Publication statusPublished - 16 Mar 2010

Keywords

  • Alphapapillomavirus
  • Carcinoma in Situ
  • Carcinoma, Squamous Cell
  • Cervical Intraepithelial Neoplasia
  • Chromosome Aberrations
  • DNA, Viral
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Genomics
  • Human papillomavirus 16
  • Humans
  • Loss of Heterozygosity
  • Oligonucleotide Array Sequence Analysis
  • Polymorphism, Single Nucleotide
  • Uterine Cervical Neoplasms
  • Vulvar Neoplasms

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