Doolittle-Hall Janet M, Cunningham Glasspoole Danielle L, Seaman William T, Webster-Cyriaque Jennifer
Department of Dental Ecology, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Oral Biology Ph.D. Program, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Cancers (Basel). 2015 Nov 10;7(4):2217-35. doi: 10.3390/cancers7040887.
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.
致癌病毒给全球带来了巨大的癌症负担。对于几种DNA肿瘤病毒而言，人类基因组整合一直与癌症发展相关。然而，与肿瘤病毒整合相关的基因组特征却鲜为人知。我们试图确定1897个易于宿主人类乳头瘤病毒（HPV）、乙肝病毒（HBV）或默克尔细胞多瘤病毒（MCPyV）的位点的基因组决定因素。将这些与HIV进行比较，HIV的酶介导整合已为人熟知。从文献和实验确定的HPV整合位点构建了一个整合位点的综合目录。对八个类别（基因、表达、开放染色质、组蛋白修饰、甲基化、蛋白质结合、染色质分割和重复序列）的特征进行评分，并与随机位点进行比较。随机森林模型确定位点分类和特征选择。HPV和HBV整合位点与脆性位点无关。MCPyV倾向于整合在感觉感知基因附近。检测到与整合相关的预测性基因组特征的独特特征。重要的是，重复序列、活跃转录区域和组蛋白修饰是常见的肿瘤病毒整合特征。
