Genome-wide Analysis of HPV Integration in Human Cancers Reveals Recurrent, Focal Genomic Instability

Overview

Journal Genome Res

Specialty Genetics

Date 2013 Nov 9

PMID 24201445

Citations 233

Authors

Keiko Akagi

Jingfeng Li

Tatevik R 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

Affiliations

Soon will be listed here.

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.

Citing Articles

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HPV integration in head and neck cancer: downstream splicing events and expression ratios linked with poor outcomes.

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