Integrated virus-host methylome analysis in head and neck squamous cell carcinoma

One in six cancers worldwide is caused by infection and human papillomavirus (HPV) is one of the main culprits. To better understand the dynamics of HPV integration and its effect on both the viral and host methylomes, we conducted whole-genome DNA methylation analysis using MeDIP-seq of HPV+ and HP...

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Bibliographic Details
Published in:Epigenetics 2013-09, Vol.8 (9), p.953-961
Main Authors: Wilson, Gareth A, Lechner, Matthias, Köferle, Anna, Caren, Helena, Butcher, Lee M, Feber, Andrew, Fenton, Tim, Jay, Amrita, Boshoff, Chris, Beck, Stephan
Format: Article
Language:English
Subjects:
Cadherins - genetics
Carcinoma, Squamous Cell - genetics
Carcinoma, Squamous Cell - metabolism
Carcinoma, Squamous Cell - virology
Cell Line, Tumor
DNA Methylation
DNA-Binding Proteins - physiology
Epigenesis, Genetic
epigenome
Genome, Human
Genome, Viral
Head and Neck Neoplasms - genetics
Head and Neck Neoplasms - metabolism
Head and Neck Neoplasms - virology
head and neck squamous cell carcinoma (HNSCC)
human papillomavirus (HPV)
Human papillomavirus 16 - genetics
Human papillomavirus 16 - physiology
Humans
methylome
Oligonucleotide Array Sequence Analysis
Oncogene Proteins, Viral - physiology
Research Paper
Squamous Cell Carcinoma of Head and Neck
Tumor Cells, Cultured
Virus Integration - genetics
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Summary:One in six cancers worldwide is caused by infection and human papillomavirus (HPV) is one of the main culprits. To better understand the dynamics of HPV integration and its effect on both the viral and host methylomes, we conducted whole-genome DNA methylation analysis using MeDIP-seq of HPV+ and HPV- head and neck squamous cell carcinoma (HNSCC). We determined the viral subtype to be HPV-16 in all cases and show that HPV-16 integrates into the host genome at multiple random sites and that this process predominantly involves the transcriptional repressor gene (E2) in the viral genome. Comparative analysis identified 453 (FDR ≤ 0.01) differentially methylated regions (DMRs) in the HPV+ host methylome. Bioinformatics characterization of these DMRs confirmed the previously reported cadherin genes to be affected but also revealed new targets for HPV-mediated methylation changes at regions not covered by array-based platforms, including the recently identified super-enhancers.
ISSN:1559-2294
1559-2308
1559-2308
DOI:10.4161/epi.25614