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Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2016

Open Access 01-12-2016 | Research

HPV16 integration probably contributes to cervical oncogenesis through interrupting tumor suppressor genes and inducing chromosome instability

Authors: Jun-Wei Zhao, Fang Fang, Yi Guo, Tai-Lin Zhu, Yun-Yun Yu, Fan-Fei Kong, Ling-Fei Han, Dong-Sheng Chen, Fang Li

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2016

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Abstract

Background

The integration of human papilloma virus (HPV) into host genome is one of the critical steps that lead to the progression of precancerous lesion into cancer. However, the mechanisms and consequences of such integration events are poorly understood. This study aims to explore those questions by studying high risk HPV16 integration in women with cervical intraepithelial neoplasia (CIN) and cervical squamous cell carcinoma (SCC).

Methods

Specifically, HPV integration status of 13 HPV16-infected patients were investigated by ligation-mediated PCR (DIPS-PCR) followed by DNA sequencing.

Results

In total, 8 HPV16 integration sites were identified inside or around genes associated with cancer development. In particular, the well-studied tumor suppressor genes SCAI was found to be integrated by HPV16, which would likely disrupt its expression and therefore facilitate the migration of tumor. On top of that, we observed several cases of chromosome translocation events coincide with HPV integration, which suggests the existence of chromosome instability. Additionally, short overlapping sequences were observed between viral derived and host derived fragments in viral-cellular junctions, indicating that integration was mediated by micro homology-mediated DNA repair pathway.

Conclusions

Overall, our study suggests a model in which HPV16 might contribute to oncogenesis not only by disrupting tumor suppressor genes, but also by inducing chromosome instability.
Appendix
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Metadata
Title
HPV16 integration probably contributes to cervical oncogenesis through interrupting tumor suppressor genes and inducing chromosome instability
Authors
Jun-Wei Zhao
Fang Fang
Yi Guo
Tai-Lin Zhu
Yun-Yun Yu
Fan-Fei Kong
Ling-Fei Han
Dong-Sheng Chen
Fang Li
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2016
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-016-0454-4

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