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Genome Res. 2014 Feb;24(2):185-99. doi: 10.1101/gr.164806.113. Epub 2013 Nov 7.

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

Author information

1
Human Cancer Genetics Program, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio 43210, USA;

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.

PMID:
24201445
PMCID:
PMC3912410
DOI:
10.1101/gr.164806.113
[Indexed for MEDLINE]
Free PMC Article

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