title: Multiple-integrations of HPV16 genome and altered transcription of viral oncogenes and cellular genes are associated with the development of cervical cancer.
abstract: The constitutive expression of the high-risk HPV E6 and E7 viral oncogenes is the major cause of cervical cancer. To comprehensively explore the composition of HPV16 early transcripts and their genomic annotation, cervical squamous epithelial tissues from 40 HPV16-infected patients were collected for analysis of papillomavirus oncogene transcripts (APOT). We observed different transcription patterns of HPV16 oncogenes in progression of cervical lesions to cervical cancer and identified one novel transcript. Multiple-integration events in the tissues of cervical carcinoma (CxCa) are significantly more often than those of low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL). Moreover, most cellular genes within or near these integration sites are cancer-associated genes. Taken together, this study suggests that the multiple-integrations of HPV genome during persistent viral infection, which thereby alters the expression patterns of viral oncogenes and integration-related cellular genes, play a crucial role in progression of cervical lesions to cervix cancer.
authors.affiliation: Department of Microbiology and Immunology, Wenzhou Medical University, Wenzhou, Zhejiang, China; Department of Pathology, Zhuji People's Hospital of Zhejiang Province, Zhuji, Zhejiang, China.
authors.forename: Xulian
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Microbiology and Immunology, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Qiaoai
authors.initials: Q
authors.lastname: Lin
authors.affiliation: Department of Microbiology and Immunology, Wenzhou Medical University, Wenzhou, Zhejiang, China; Fuda Cancer Hospital Affiliated to the Medical College of Jinan University, Guangzhou, Guangdong, China.
authors.forename: Mao
authors.initials: M
authors.lastname: Lin
authors.affiliation: Department of Obstetrics and Gynecology, Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Duan
authors.affiliation: Institute of Molecular Virology and Immunology, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Lulu
authors.initials: L
authors.lastname: Ye
authors.affiliation: Department of Microbiology and Immunology, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.affiliation: School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Xiangmin
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Microbiology and Immunology, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Lifang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Institute of Molecular Virology and Immunology, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Xue
mesh_terms: D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D016679:Genome, Viral; D052162:Human papillomavirus 16 / Q000378:metabolism*; D006801:Humans; D015513:Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D030361:Papillomavirus Infections / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D014764:Viral Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D015513:Oncogene Proteins; D014764:Viral Proteins