title: Genome-wide analysis of HPV integration in human cancers reveals recurrent, focal genomic instability.
abstract: Genomic instability is a hallmark of human cancers, including the 5% caused by human papillomavirus (HPV). Here we report a striking association between HPV integration and adjacent host genomic structural variation in human cancer cell lines and primary tumors. Whole-genome sequencing revealed HPV integrants flanking and bridging extensive host genomic amplifications and rearrangements, including deletions, inversions, and chromosomal translocations. We present a model of "looping" by which HPV integrant-mediated DNA replication and recombination may result in viral-host DNA concatemers, frequently disrupting genes involved in oncogenesis and amplifying HPV oncogenes E6 and E7. Our high-resolution results shed new light on a catastrophic process, distinct from chromothripsis and other mutational processes, by which HPV directly promotes genomic instability.
authors.affiliation: Human Cancer Genetics Program, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio 43210, USA;
authors.forename: Keiko
authors.initials: K
authors.lastname: Akagi
authors.forename: Jingfeng
authors.initials: J
authors.lastname: Li
authors.forename: Tatevik R
authors.initials: TR
authors.lastname: Broutian
authors.forename: Hesed
authors.initials: H
authors.lastname: Padilla-Nash
authors.forename: Weihong
authors.initials: W
authors.lastname: Xiao
authors.forename: Bo
authors.initials: B
authors.lastname: Jiang
authors.forename: James W
authors.initials: JW
authors.lastname: Rocco
authors.forename: Theodoros N
authors.initials: TN
authors.lastname: Teknos
authors.forename: Bhavna
authors.initials: B
authors.lastname: Kumar
authors.forename: Danny
authors.initials: D
authors.lastname: Wangsa
authors.forename: Dandan
authors.initials: D
authors.lastname: He
authors.forename: Thomas
authors.initials: T
authors.lastname: Ried
authors.forename: David E
authors.initials: DE
authors.lastname: Symer
authors.forename: Maura L
authors.initials: ML
authors.lastname: Gillison
mesh_terms: D004261:DNA Replication / Q000235:genetics*; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D042822:Genomic Instability; D052162:Human papillomavirus 16 / Q000235:genetics* / Q000254:growth & development; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology / Q000821:virology; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism; D050725:Papillomavirus E7 Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D016662:Virus Integration / Q000235:genetics
chemical_list: D004279:DNA, Viral; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16