title: Meta-Analysis of DNA Tumor-Viral Integration Site Selection Indicates a Role for Repeats, Gene Expression and Epigenetics.
abstract: Oncoviruses cause tremendous global cancer burden. For several DNA tumor viruses, human genome integration is consistently associated with cancer development. However, genomic features associated with tumor viral integration are poorly understood. We sought to define genomic determinants for 1897 loci prone to hosting human papillomavirus (HPV), hepatitis B virus (HBV) or Merkel cell polyomavirus (MCPyV). These were compared to HIV, whose enzyme-mediated integration is well understood. A comprehensive catalog of integration sites was constructed from the literature and experimentally-determined HPV integration sites. Features were scored in eight categories (genes, expression, open chromatin, histone modifications, methylation, protein binding, chromatin segmentation and repeats) and compared to random loci. Random forest models determined loci classification and feature selection. HPV and HBV integrants were not fragile site associated. MCPyV preferred integration near sensory perception genes. Unique signatures of integration-associated predictive genomic features were detected. Importantly, repeats, actively-transcribed regions and histone modifications were common tumor viral integration signatures.
authors.affiliation: Department of Dental Ecology, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. doolittl@email.unc.edu.
authors.forename: Janet M
authors.initials: JM
authors.lastname: Doolittle-Hall
authors.affiliation: Oral Biology Ph.D. Program, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Danielle_Cunningham@unc.edu.
authors.forename: Danielle L
authors.initials: DL
authors.lastname: Cunningham Glasspoole
authors.affiliation: Lineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Todd_Seaman@unc.edu.
authors.forename: William T
authors.initials: WT
authors.lastname: Seaman
authors.affiliation: Department of Dental Ecology, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Jennifer_Cyriaque@unc.edu.|Lineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Jennifer_Cyriaque@unc.edu.|Department of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Jennifer_Cyriaque@unc.edu.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Webster-Cyriaque
keywords: HBV; HIV; HPV; MCPyV; viral integration