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

• Published in: British journal of cancer Vol. 102; no. 6; pp. 1044 - 1051
• Main Authors: Purdie, K J, Harwood, C A, Gibbon, K, Chaplin, T, Young, B D, Cazier, J B, Singh, N, Leigh, I M, Proby, C M
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 16-03-2010; Nature Publishing Group
• Subjects: 631/208/2489/1381; 631/326/596/2560; 631/61/191/2018; 692/699/2768; Alphapapillomavirus - physiology; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Carcinoma in Situ - etiology; Carcinoma in Situ - genetics; Carcinoma in Situ - virology; Carcinoma, Squamous Cell - etiology; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - virology; Cervical Intraepithelial Neoplasia - genetics; Chromosome Aberrations; DNA, Viral - analysis; Drug Resistance; Epidemiology; Female; Gene Expression Profiling - methods; Gene Expression Regulation, Neoplastic; Genomics - methods; Human papillomavirus 16 - physiology; Humans; Infectious diseases; Loss of Heterozygosity; Medical sciences; Molecular Diagnostics; Molecular Medicine; Oligonucleotide Array Sequence Analysis; Oncology; Polymorphism, Single Nucleotide; Tumors; Uterine Cervical Neoplasms - genetics; Viral diseases; Vulvar Neoplasms - etiology; Vulvar Neoplasms - genetics; Vulvar Neoplasms - virology; VIN; chromosome aberration; SNP array; VSCC; vulva; human papillomavirus; Chromosomal aberration; High resolution; Vulva; Papovaviridae; Malignant tumor; Infection; Papillomavirus; Virus; Human papillomavirus; Cancerology; Viral disease; Genome; Cancer
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6605589

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.