Literature Information
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PubMed PMID
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18922896
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Published year
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2008 |
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Journal
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Cancer research |
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Title
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Characterization of naturally occurring HPV16 integration sites isolated from cervical keratinocytes under noncompetitive conditions. |
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Author
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Dall KL,Scarpini CG,Roberts I,Winder DM,Stanley MA,Muralidhar B,Herdman MT,Pett MR,Coleman N |
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Evidence
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As the high-risk human papillomavirus (HPV) integrants seen in anogenital carcinomas represent the end-point of a clonal selection process, we used the W12 model to study the naturally occurring integration events that exist in HPV16-infected cervical keratinocytes before integrant selection. We found that integration can occur at any time during episome maintenance, providing biological support for epidemiologic observations that persistent HPV infection is a major risk factor in cervical carcinogenesis. Of 24 different integration sites isolated from a single nonclonal population of W12, 12 (50%) occurred within chromosome bands containing a common fragile site (CFS), similar to observations for selected integrants in vivo. We further observed that local DNA rearrangements occur frequently and rapidly after the integration event. The majority of integrants were in chromosome bands containing a cancer-associated coding gene or microRNA, indicating that integration occurs commonly in these regions, regardless of selective pressure. The cancer-associated genes were generally a considerable distance from the integration site, and there was no evidence for altered expression of nine strong candidate genes. These latter observations do not support an important role for HPV16 integration in causing insertional mutagenesis.
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HPV VIS Detail Information