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Genome-wide analysis of HPV integration in human cancers reveals recurrent, focal genomic instability

2013; Cold Spring Harbor Laboratory Press; Volume: 24; Issue: 2 Linguagem: Inglês

10.1101/gr.164806.113

1549-5469

Keiko Akagi, Jingfeng Li, Tatevik Broutian, Hesed Padilla‐Nash, Weihong Xiao, Bo Jiang, James W. Rocco, Theodoros N. Teknos, Bhavna Kumar, Danny Wangsa, Dandan He, Thomas Ried, David E. Symer, Maura L. Gillison,

Cancer Genomics and Diagnostics

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.