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

Autor: Tai-Lin Zhu, Fang Fang, Yun-Yun Yu, Fang Li, Yi Guo, Dong-Sheng Chen, Junwei Zhao, Lingfei Han, Fan-Fei Kong
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
HPV16
Adult
Cancer Research
Cervical oncogenesis
viruses
Virus Integration
Integration
Uterine Cervical Neoplasms
Chromosomal translocation
Biology
medicine.disease_cause
Cervical intraepithelial neoplasia
lcsh:RC254-282
Translocation
Genetic
law.invention
03 medical and health sciences
law
Chromosome instability
Chromosomal Instability
Protein Interaction Mapping
medicine
Humans
Gene
Genetics
Human papillomavirus 16
Research
Cancer
virus diseases
DNA Repair Pathway
Sequence Analysis
DNA
Middle Aged
medicine.disease
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Uterine Cervical Dysplasia
female genital diseases and pregnancy complications
030104 developmental biology
Oncology
DNA
Viral
Cancer research
Carcinoma
Squamous Cell
Suppressor
Female
Carcinogenesis
Transcription Factors
Zdroj: Journal of Experimental & Clinical Cancer Research : CR
Journal of Experimental & Clinical Cancer Research, Vol 35, Iss 1, Pp 1-14 (2016)
ISSN: 1756-9966
0392-9078
Popis: 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. Electronic supplementary material The online version of this article (doi:10.1186/s13046-016-0454-4) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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