Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

HPV integration generates cellular super enhancer and functions as ecDNA to regulate genome-wide transcription

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE195631 | GEO | 2023/04/19

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Recurrent Integration of Human Papillomavirus Genomes at Transcriptional Regulatory Hubs

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

HPV genome expression at invasive cervical carcinomas infected by multiple HPV genotypes

Project description:Multiple HPV genotypes infection is frequently detected in HPV+ cervical lesions, however it is not well stablished how is the different viral interaction during the carcinogenic process. Here we carried out a comprehensive study to characterize the multiple HPV genome expression and integration by RNA-Seq analysis in 19 invasive cervical carcinomas with HPV coinfections. Analysis of tumoral DNA by a hybridization kit indicated multi-infection ranging from 2 to 6 different HPV genotypes, without a preferential species coinfection. The expression analysis showed that a single HPV genotype preferentially expressed its genome, might indicating a competition between the infecting virus. Finally, the search for HPV/human chimeric transcripts indicated integration from just one HPV in almost all samples, corroborating the expression findings.

2021-07-28 | GSE144293 | GEO

Oncogenic extrachromosomal DNA functions as mobile enhancers to globally amplify chromosomal transcription

Project description:Extrachromosomal, circular DNA (ecDNA) is emerging as a prevalent yet less characterized oncogenic alteration in cancer genomes. We leverage ChIA-PET and ChIA-Drop chromatin interaction assays to characterize genome-wide ecDNA-mediated chromatin contacts that impact transcriptional programs in cancers. ecDNAs in glioblastoma patient-derived neurosphere and prostate cancer cell cultures are marked by widespread intra-ecDNA and genome-wide chromosomal interactions. ecDNA-chromatin contact foci are characterized by broad and high-level H3K27ac signals converging predominantly on chromosomal genes of increased expression levels. Prostate cancer cells harboring synthetic ecDNA circles composed of characterized enhancers result in the genome-wide activation of chromosomal gene transcription. Deciphering the chromosomal targets of ecDNAs at single-molecule resolution reveals an association with actively expressed oncogenes spatially clustered within ecDNA-directed interaction networks. Our results suggest that ecDNA can function as mobile transcriptional enhancers to promote tumor progression and manifest a potential synthetic aneuploidy mechanism of transcription control in cancer.

2021-04-08 | GSE124769 | GEO

Differentially expressed gene profiles according to physical status of human papillomavirus integration in cervical cancer

2013-07-28 | GSE49288 | GEO

Differentially expressed gene profiles according to physical status of human papillomavirus integration in cervical cancer

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

HPV integration generates cellular super enhancer and functions as ecDNA to regulate genome-wide transcription

Project description:HPV integration generates cellular super enhancer and functions as ecDNA to regulate genome-wide transcription

| PRJNA801595 | ENA

Genomic Sequencing of Cervical Cancers

Project description:<p>Cervical cancer is responsible for 10-15% of cancer related deaths in women worldwide. The etiological role of infection with high-risk human papilloma viruses (HPV) in carcinomas of the cervix is well established. In general, the development of cervical carcinomas follows a progression from persistent HPV infection through precancerous lesions to invasive cancer. Previous studies have implicated somatic mutations in PIK3CA, PTEN, TP53, STK11 and KRAS as well as chromosome-arm level copy number alterations in the pathogenesis of cervical carcinomas. Here, we report whole exome sequencing analysis of 118 cervical carcinoma-normal paired samples from patients in Norway and Mexico, as well as transcriptome sequencing of 80 cases and whole genome sequencing of 13 tumor-normal pairs. Novel somatic mutations include recurrent E322K substitutions in the MAPK1 gene encoding the ERK2 kinase and inactivating mutations in the HLA-B gene. In addition, recurrent somatic mutations in FBXW7, EP300, and NFE2L2 are novel in the context of primary cervical carcinomas. Analysis of HPV integration sites revealed recurrent integration into the RAD51B locus as well as co-occurrence of HPV genome integration and copy number gains within several genomic loci. These findings shed new light on the pathogenesis of cervical carcinomas and suggest potential novel therapeutic targets.</p>

| phs000600 | dbGaP

human plasma sample parallel reaction monitoring

Project description:Women are vulnerable to cervical diseases including normal control, HSIL and early stage cervical carcinoma . The parallel reaction monitoring mass spectrometry (PRM-MS) were used to qualitatively and quantitatively analyze the candidate differential proteins identified in our previous studies and to link them with HPV status. The integration of HPV status with candidate serum markers is expected to efficiently narrow down the high risk population and provide sufficient clinical information for early diagnosis and effective therapy.

2021-09-09 | PXD022756 | Pride

Whole genome tiling path array CGH analysis of segmental copy number alterations in cervical cancer cells

Project description:Cervical cancer is the second most common malignancy in women worldwide, with high risk subtypes of human papillomavirus (HPV) constituting the major etiological agent. However, only a small percentage of women infected by the virus develop disease suggesting that additional host genetic alterations are necessary for disease progression. In this study we examined the genomes of a panel of commonly used model cervical cancer cell lines using a recently developed whole genome tiling path array for CGH analysis. Detailed analysis of genomic profiles enabled the detection of many novel aberrations which may have been missed by conventional cytogenetic methods. In total, 27 minimal regions of recurrent copy number alteration were identified that are potentially involved in tumorigenesis. Interestingly, fine mapping of the 3q gain, which is associated with the progression of precursor lesions to invasive cervical cancer, identified a minimal region of alteration harboring genes distinct from previous candidates. Novel regions of gene amplification, including the co-amplification of both the Birc and MMP gene clusters on 11q22, were also evident. Lastly, characterization of genomic structure at sites of HPV integration identified the copy number gain of host cellular sequences between the viral-host genomic boundaries in both SiHa and SW756, suggesting a direct role for HPV integration in the development of genetic abnormalities that initiate cervical cancer. This work represents the highest resolution look at a cervical cancer genome to date and offers definitive characterization of the alteration status of these cancer genomes. Keywords: array CGH, copy number, cervical cancer, genetic alterations, HPV integration, 3q

2007-06-12 | GSE5049 | GEO

Oncogene expression from extrachromosomal DNA is driven by copy number amplification and does not require spatial clustering in glioblastoma stem cells

Project description:Extrachromosomal DNA (ecDNA) are frequently observed in human cancers and are responsible for high levels of oncogene expression. In glioblastoma (GBM), ecDNA copy number correlates with poor prognosis. It is hypothesized that their copy number, size and chromatin accessibility facilitate clustering of ecDNA and colocalization with transcriptional hubs, and that this underpins their elevated transcriptional activity. Here, we use super-resolution imaging and quantitative image analysis to evaluate GBM stem cells harboring distinct ecDNA species (EGFR, CDK4, PDGFR). We found no evidence that ecDNA routinely cluster with one another or closely interact with transcriptional hubs. Cells with EGFR-containing ecDNA have increased EGFR transcriptional output, but transcription per gene copy was similar in ecDNA compared to the endogenous chromosomal locus. These data suggest that it is the increased copy number of oncogene-harboring ecDNA that primarily drives high levels of oncogene transcription, rather than specific interactions of ecDNA with each other or with high concentrations of the transcriptional machinery.

2022-11-11 | GSE215420 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data