Integrative sequencing analysis of a metastatic cervical carcinoma patient reveals human papillomavirus 18 integration
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PROVIDER: PRJNA208767 | ENA |
REPOSITORIES: ENA
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Project description:Integration of human papillomavirus (HPV) DNA into the host genome is a critical aetiological event in the progression from normal cervix to intraepithelial neoplasm, and finally to invasive cervical cancer. In this study, we want to know how HPV DNA physical status relates to treatment outcome for cervical carcinomas.
2013-07-28 | GSE49288 | GEO
Project description:Integration of human papillomavirus (HPV) DNA into the host genome is a critical aetiological event in the progression from normal cervix to intraepithelial neoplasm, and finally to invasive cervical cancer. In this study, we want to know how HPV DNA physical status relates to treatment outcome for cervical carcinomas. Cervical cancer samples were compared with normal sample. And also, we divided 39 cervical cancer patients into four groups according to HPV DNA physical status and investigated differentially expressed gene profiles in these groups using Agilent two-color experiment.
2013-07-28 | E-GEOD-49288 | biostudies-arrayexpress
Project description:Oncogenic human papillomavirus (HPV) genomes are often integrated into host chromosomes in HPV-associated cancers. HPV genomes are integrated either as a single copy, or as tandem repeats of viral DNA interspersed with, or without, host DNA. Integration occurs frequently in common fragile sites susceptible to tandem repeat formation, and the flanking or interspersed host DNA often contains transcriptional enhancer elements. When co-amplified with the viral genome, these enhancers can form super-enhancer-like elements that drive high viral oncogene expression. Here, we compiled highly curated datasets of HPV integration sites in cervical (CESC) and head and neck squamous cell carcinoma (HNSCC) cancers and assessed the number of breakpoints, viral transcriptional activity, and host genome copy number at each insertion site. Tumors frequently contained multiple distinct HPV integration sites, but often only one “driver” site that expressed viral RNA. Since common fragile sites and active enhancer elements are cell-type specific, we mapped these regions in cervical cell lines using FANCD2 and Brd4/H3K27ac ChIP-seq, respectively. Large enhancer clusters, or super-enhancers, were also defined using the Brd4/H3K27ac ChIP-seq dataset. HPV integration breakpoints were enriched at both FANCD2-associated fragile sites, and enhancer-rich regions, and frequently showed adjacent focal DNA amplification in CESC samples. We identified recurrent integration “hotspots” that were enriched for super-enhancers, some of which function as regulatory hubs for cell-identity genes. We propose that during persistent infection, extrachromosomal HPV minichromosomes associate with these transcriptional epicenters, and accidental integration could promote viral oncogene expression and carcinogenesis.
2021-09-01 | GSE183048 | GEO
Project description:Human papillomavirus (HPV) genome integration into the host genome, blocking E2 expression and leading to overexpression of E6 and E7 viral oncogenes, is considered a major step in cervical cancer development. In high-risk HPVs, E6 and E7 oncogenes are expressed as a bicistronic pre-mRNA, with alternative splicing producing the ultimate mRNAs required for E6 and E7 translation. Given the number of alternative donor and acceptor splicing sites, ten E6/E7 different alternative transcripts might be formed for HPV16 and three for HPV18, although only six isoforms have been previously reported for HPV16. In the present work, we employ high-throughput sequencing of invasive cervical cancer transcriptome (RNA-Seq) to characterize the expression of the HPV genome in 24 invasive cervical cancers associated with HPV16 and HPV18 single infections. Based on high-resolution transcriptional maps, we herein report three viral gene expression patterns which might be associated with the presence of the viral genome in episomal and/or integrated stages. Alternative mRNAs splicing isoforms coding for E6 and E7 oncoproteins were characterized and quantified, and two novel isoforms were identified. Three major isoforms (E6*I, E6*II, and E6+E7) were detected for HPV16 and two for HPV18 (E6*I and E6+E7). Minor transcript isoforms, including the novel ones, were very rare in some tumor samples or were not detected. Our data suggested that minor transcript isoforms of E6/E7 do not play a relevant role in cervical cancer.
2019-08-06 | GSE91065 | GEO
Project description:Integration of high-risk human papillomavirus (HRHPV) into the host genome is a key event in cervical neoplastic progression. Integration is associated with deregulated expression of the viral oncogenes E6 and E7 and acquisition of a selective growth advantage.
2007-11-11 | E-GEOD-4289 | biostudies-arrayexpress
Project description:Human papillomavirus (HPV) integration is a critical step in cervical cancer development, while the oncogenic mechanism in genome-wide transcriptional level is still poorly understood. In this study, we employed integrative analysis on multi-omics data of cervical cancer cell lines. Through HPV integration detection, super enhancer (SE) identification, SE-associated gene expression and extrachromosomal DNA (ecDNA) investigation, we aimed to explore the genome-wide transcriptional influence of HPV integration. We identified 5 high-ranking cellular super enhancers generated by HPV integration (the HPV breakpoint induced cellular super enhancers, BP-cSE), leading to intra-chromosomal and inter-chromosomal regulations of chromosomal genes. The pathway analysis showed the dysregulated chromosomal genes were correlated to cervical cancer associated pathways. Importantly, we demonstrated that BP-cSE existed in the HPV-host ecDNA, explaining above transcription alterations. Our results suggest that HPV integration generates cellular super enhancers and functions as ecDNA to regulate unconstraint transcription, expanding the tumorigenic mechanism of HPV integration and providing insights of developing new diagnostic and therapeutic strategies.
2023-04-19 | GSE195631 | GEO
Project description:Our previous study implied a correlation of inhibitors of differentiation-1 (Id-1) to cervical cancer development. However, how Id-1 contributes to cervical carcinogenesis is unknown. In the present study, we investigated the role of Id-1 in transforming cervical cells with an in vitro transformation model. The human papillomavirus (HPV) immortalized cervical epithelial cells (H8) were successfully transformed by exposure to the carcinogen N-nitrosopyrrolidine (NPYR). The results showed that both Id-1 RNA and protein expression were significantly increased in transformed H8 cells, suggesting a possible role of Id-1 in cervical cell transformation. Ectopic expression of Id-1 in H8 cells potentiated NPYR-induced cell transformation. In contrast, silencing of Id-1 suppressed NPYR-induced H8 cell transformation. A cDNA microarray assay was performed, which identified suggested potential cell signaling pathways for NPYR-induced H8 cell transformation. The results suggest that Id-1 plays an oncogenic role in the cervix, which sheds light on cervical cancer development and implies potential target for cervical cancer prevention and therapy.
2013-05-11 | GSE46842 | GEO
Project description:Integrative sequencing analysis of a metastatic cervical carcinoma patient reveals human papillomavirus 18 integration
| PRJNA208768 | ENA
Project description:Cervical cancer is the one of the most common cancer type among women worldwide, with Human Papillomavirus (HPV) playing a causal role in this disease. We applied a novel integrative approach to understand the disease process and find its major drivers. We performed a meta-analysis of gene expression and chromosomal aberration studies comprising data on over 500 patients for the reconstruction of a regulatory meta-network. We found that two sub-networks representing cell cycle and antiviral response (largely involving interferon pathways) were driven by chromosomal amplifications of key regulator genes. In the majority of patients, the two types of drivers were located in the same regions of chromosomal aberrations on 3q, 1q and 1p suggesting that a synergistic effect of both processes is necessary for cervical oncogenesis. In addition, our results revealed a cause of antiviral response in the tumor supporting a model of cervical carcinogenesis in which the loss of episomal HPV mediated by immune response promotes the expression of integrated viral oncogenes and tumor progression. This series is a part of meta-analysis on gene expression in cervical cancer
2011-12-29 | GSE26342 | GEO
Project description:Cervical cancer is the one of the most common cancer type among women worldwide, with Human Papillomavirus (HPV) playing a causal role in this disease. We applied a novel integrative approach to understand the disease process and find its major drivers. We performed a meta-analysis of gene expression and chromosomal aberration studies comprising data on over 500 patients for the reconstruction of a regulatory meta-network. We found that two sub-networks representing cell cycle and antiviral response (largely involving interferon pathways) were driven by chromosomal amplifications of key regulator genes. In the majority of patients, the two types of drivers were located in the same regions of chromosomal aberrations on 3q, 1q and 1p suggesting that a synergistic effect of both processes is necessary for cervical oncogenesis. In addition, our results revealed a cause of antiviral response in the tumor supporting a model of cervical carcinogenesis in which the loss of episomal HPV mediated by immune response promotes the expression of integrated viral oncogenes and tumor progression. This series is a part of meta-analysis on gene expression in cervical cancer Forty cervical cancer biopsies and twenty normal adjacent tissue samples were obtained from patients with cervical squamous cell carcinomas. Twelve tumor samples were hybridized as pools of two samples, due to RNA quantity limitations. So, in total, there are 34 cervical cancer and 20 normal sample arrays. We used an internal reference design, where the reference RNA sample consisted of a pool of amplified RNAs from cervical cancer biopsies.
2011-12-29 | E-GEOD-26342 | biostudies-arrayexpress