Frequent genomic structural alterations at HPV insertion sites in cervical carcinoma
- 19 March 2010
- journal article
- research article
- Published by Wiley in The Journal of Pathology
- Vol. 221 (3), 320-330
- https://doi.org/10.1002/path.2713
Abstract
To investigate whether integration of HPV DNA in cervical carcinoma is responsible for structural alterations of the host genome at the insertion site, a series of 34 primary cervical carcinomas and eight cervical cancer-derived cell lines were analysed. DNA copy number profiles were assessed using the Affymetrix GeneChip Human Mapping 250K Sty array. HPV 16, 18 or 45 integration sites were determined using the DIPS-PCR technique. The genome status at integration sites was classified as follows: no change, amplification, transition normal/gain, normal/loss or gain/LOH. A single HPV integration site was found in 34 cases; two sites were found in seven cases; and three sites in one case (51 sites). Comparison between integration sites and DNA copy number profiles showed that the genome status was altered at 17/51 (33%) integration sites, corresponding to 16/42 cases (38%). Alterations detected were amplification in nine cases, transition normal/loss in four cases, normal/gain in three cases, and gain/LOH in one case. A highly significant association was found between genomic rearrangement and integration of HPV DNA (p < 10−10). Activation of the replication origin located in viral integrated sequences in a cell line derived from one of the primary cervical carcinomas induced an increase of the amplification level of both viral and cellular DNA sequences flanking the integration locus. This mechanism may be implicated in the triggering of genome amplification at the HPV integration site in cervical carcinoma. Structural alterations of the host genome are frequently observed at the integration site of HPV DNA in cervical cancer and may act in oncogenesis. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.Keywords
Funding Information
- La Maison Goyard
- luxury luggage-maker
This publication has 35 references indexed in Scilit:
- Mechanism of Genomic Instability in Cells Infected with the High-Risk Human PapillomavirusesPLoS Pathogens, 2009
- Different outcome of invasive cervical cancer associated with high‐risk versus intermediate‐risk HPV genotypeInternational Journal of Cancer, 2008
- The Majority of Viral-Cellular Fusion Transcripts in Cervical Carcinomas Cotranscribe Cellular Sequences of Known or Predicted GenesCancer Research, 2008
- ITALICS: an algorithm for normalization and DNA copy number calling for Affymetrix SNP arraysBioinformatics, 2008
- Type-Dependent Integration Frequency of Human Papillomavirus Genomes in Cervical LesionsCancer Research, 2008
- An increase in DNA double‐strand breaks, induced by Ku70 depletion, is associated with human papillomavirus 16 episome loss and de novo viral integration eventsThe Journal of Pathology, 2007
- Genomic instability of the host cell induced by the human papillomavirus replication machineryThe EMBO Journal, 2007
- Increased gene copy numbers at chromosome 20q are frequent in both squamous cell carcinomas and adenocarcinomas of the cervixThe Journal of Pathology, 2006
- Analysis of array CGH data: from signal ratio to gain and loss of DNA regionsBioinformatics, 2004
- Papillomaviruses and cancer: from basic studies to clinical applicationNature Reviews Cancer, 2002