期刊
GENOME RESEARCH
卷 24, 期 2, 页码 185-199出版社
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gr.164806.113
关键词
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资金
- Ohio State University Comprehensive Cancer Center
- Ohio Supercomputer Center [PAS0425]
- Ohio Cancer Research Associate grant [GRT00024299]
- Oral Cancer Foundation
- Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research
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.
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