RT Journal A1 Akagi, Keiko A1 Li, Jingfeng A1 Broutian, Tatevik R A1 Padilla-Nash, Hesed A1 Xiao, Weihong A1 Jiang, Bo A1 Rocco, James W A1 Teknos, Theodoros N A1 Kumar, Bhavna A1 Wangsa, Danny A1 He, Dandan A1 Ried, Thomas A1 Symer, David E A1 Gillison, Maura L T1 Genome-wide analysis of HPV integration in human cancers reveals recurrent, focal genomic instability JF Genome Research JO Genome Research YR 2013 FD November 07 DO 10.1101/gr.164806.113 SP gr.164806.113 UL http://genome.cshlp.org/content/early/2013/11/05/gr.164806.113.abstract AB 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.