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

Integrated virus-host methylome analysis in head and neck squamous cell carcinoma
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 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.
DNA methylation, Epigenome, Head and neck squamous cell cancer (HNSCC), Human papillomavirus (HPV), Methylome
1559-2294
953-961
Wilson, GA
7dc2682a-71fa-428f-91a5-a5100d62db77
Lechner, M
19c72359-7dc0-435c-817a-f67d4956656f
Köferle, A
187202ec-9c03-4a69-81f5-dc34157d66c0
Carén, H
ab78fcb8-66b6-4222-af7c-975f099bb39c
Butcher, LM
7744895f-2b21-42e3-80fe-17272f22c75e
Feber, A
cdc62c70-e4c3-4a70-8eff-515a6eaf895b
Fenton, TR
087260ba-f6a1-405a-85df-099d05810a84
Jay, A
78312454-2b2b-4be8-bafa-506a2f8829c2
Boshoff, C
7a31a970-ff94-4ea6-b24a-dab87ae08074
Beck, S
67ec6ea3-2aed-415b-894b-55eefb959479
Wilson, GA
7dc2682a-71fa-428f-91a5-a5100d62db77
Lechner, M
19c72359-7dc0-435c-817a-f67d4956656f
Köferle, A
187202ec-9c03-4a69-81f5-dc34157d66c0
Carén, H
ab78fcb8-66b6-4222-af7c-975f099bb39c
Butcher, LM
7744895f-2b21-42e3-80fe-17272f22c75e
Feber, A
cdc62c70-e4c3-4a70-8eff-515a6eaf895b
Fenton, TR
087260ba-f6a1-405a-85df-099d05810a84
Jay, A
78312454-2b2b-4be8-bafa-506a2f8829c2
Boshoff, C
7a31a970-ff94-4ea6-b24a-dab87ae08074
Beck, S
67ec6ea3-2aed-415b-894b-55eefb959479

Wilson, GA, Lechner, M, Köferle, A, Carén, H, Butcher, LM, Feber, A, Fenton, TR, Jay, A, Boshoff, C and Beck, S (2013) Integrated virus-host methylome analysis in head and neck squamous cell carcinoma. Epigenetics, 8 (9), 953-961. (doi:10.4161/epi.25614).

Record type: Article

Abstract

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.

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More information

Accepted/In Press date: 2 July 2013
Published date: 18 July 2013
Additional Information: copyright 2013 Landes Bioscience. under the Creative Commons Attribution-NonCommercial 3.0 Unported License (http://creativecommons.org/licenses/by-nc/3.0).
Keywords: DNA methylation, Epigenome, Head and neck squamous cell cancer (HNSCC), Human papillomavirus (HPV), Methylome

Identifiers

Local EPrints ID: 453953
URI: http://eprints.soton.ac.uk/id/eprint/453953
ISSN: 1559-2294
PURE UUID: 18eba9dd-66d9-47ba-be04-a14998c51ef9
ORCID for TR Fenton: ORCID iD orcid.org/0000-0002-4737-8233

Catalogue record

Date deposited: 26 Jan 2022 17:48
Last modified: 17 Mar 2024 04:11

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Contributors

Author: GA Wilson
Author: M Lechner
Author: A Köferle
Author: H Carén
Author: LM Butcher
Author: A Feber
Author: TR Fenton ORCID iD
Author: A Jay
Author: C Boshoff
Author: S Beck

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