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

Journal of Experimental & Clinical Cancer Research

Tai-Lin Zhu¹  Dong-Sheng Chen²  Fan-Fei Kong³  Jun-Wei Zhao³  Fang Fang³  Yi Guo³  Ling-Fei Han³  Yun-Yun Yu³  Fang Li³ 

[1] Abbey College Cambridge, Homerton Gardens;Department of Genetics, University of Cambridge;Department of Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine;

关键词: HPV16;    Integration;    Cervical oncogenesis;    Chromosome instability;   

DOI  :  10.1186/s13046-016-0454-4

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown