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.
Original language | English (US) |
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Pages (from-to) | 185-199 |
Number of pages | 15 |
Journal | Genome research |
Volume | 24 |
Issue number | 2 |
DOIs | |
State | Published - Feb 2014 |
ASJC Scopus subject areas
- Genetics
- Genetics(clinical)