title: Integrated virus-host methylome analysis in head and neck squamous cell carcinoma.
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.
authors.affiliation: Medical Genomics; UCL Cancer Institute; University College London; London, UK.
authors.forename: Gareth A
authors.initials: GA
authors.lastname: Wilson
authors.forename: Matthias
authors.initials: M
authors.lastname: Lechner
authors.forename: Anna
authors.initials: A
authors.lastname: Köferle
authors.forename: Helena
authors.initials: H
authors.lastname: Caren
authors.forename: Lee M
authors.initials: LM
authors.lastname: Butcher
authors.forename: Andrew
authors.initials: A
authors.lastname: Feber
authors.forename: Tim
authors.initials: T
authors.lastname: Fenton
authors.forename: Amrita
authors.initials: A
authors.lastname: Jay
authors.forename: Chris
authors.initials: C
authors.lastname: Boshoff
authors.forename: Stephan
authors.initials: S
authors.lastname: Beck
mesh_terms: D015820:Cadherins / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000821:virology*; D045744:Cell Line, Tumor; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000502:physiology; D044127:Epigenesis, Genetic; D015894:Genome, Human; D016679:Genome, Viral; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000821:virology*; D052162:Human papillomavirus 16 / Q000235:genetics* / Q000502:physiology; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D009856:Oncogene Proteins, Viral / Q000502:physiology; D000077195:Squamous Cell Carcinoma of Head and Neck; D014407:Tumor Cells, Cultured; D016662:Virus Integration / Q000235:genetics*
chemical_list: D015820:Cadherins; D004268:DNA-Binding Proteins; C054855:E2 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral
keywords: DNA methylation; epigenome; head and neck squamous cell carcinoma (HNSCC); human papillomavirus (HPV); methylome