In:
Genome Research, Cold Spring Harbor Laboratory, Vol. 24, No. 2 ( 2014-02), p. 185-199
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.
Type of Medium:
Online Resource
ISSN:
1088-9051
DOI:
10.1101/gr.164806.113
Language:
English
Publisher:
Cold Spring Harbor Laboratory
Publication Date:
2014
detail.hit.zdb_id:
1483456-X
SSG:
12
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