Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Human papillomavirus 42 is an oncogenic driver in Digital Papillary Adenocarcinoma [full_genomes]

ABSTRACT: The skin serves as a barrier to the environment and is constantly exposed to viral pathogens. However, whether and how viral pathogens contribute to oncogenesis of rare skin cancers has not been explored. We analyzed 18 skin cancers by exploiting sparse off-target reads from commonly available next-generation sequencing data and identify human papillomavirus 42 (HPV42) reads in digital papillary adenocarcinoma (DPA). We show that HPV42 recapitulates the molecular hallmarks of oncogenic HPVs and shares a conserved transcriptomic fingerprint of HPV-transformation. Finally, we show that HPV42 relies on established cellular targets of oncogenic HPVs for its transforming activity. The discovery of HPV42 as a novel oncogenic driver highlights the utility of next-generation sequencing data for the discovery of novel pathogen-disease associations and suggests expansion of current HPV vaccination programs to reduce the cancer burden in humans.

ORGANISM(S): Homo sapiens

PROVIDER: GSE196216 | GEO | 2022/10/10

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Human papillomavirus 42 is an oncogenic driver in Digital Papillary Adenocarcinoma [transductions]

Project description:The skin serves as a barrier to the environment and is constantly exposed to viral pathogens. However, whether and how viral pathogens contribute to oncogenesis of rare skin cancers has not been explored. We analyzed 18 skin cancers by exploiting sparse off-target reads from commonly available next-generation sequencing data and identify human papillomavirus 42 (HPV42) reads in digital papillary adenocarcinoma (DPA). We show that HPV42 recapitulates the molecular hallmarks of oncogenic HPVs and shares a conserved transcriptomic fingerprint of HPV-transformation. Finally, we show that HPV42 relies on established cellular targets of oncogenic HPVs for its transforming activity. The discovery of HPV42 as a novel oncogenic driver highlights the utility of next-generation sequencing data for the discovery of novel pathogen-disease associations and suggests expansion of current HPV vaccination programs to reduce the cancer burden in humans.

2022-10-10 | GSE196217 | GEO

Human papillomavirus 42 is an oncogenic driver in Digital Papillary Adenocarcinoma [tumors]

2022-10-10 | GSE196215 | GEO

Quantitative TMT-MS of HPV42, HPV16 or empty vector transduced keratinocytes.

Project description:The skin serves as a barrier to the environment and is constantly exposed to viral pathogens. Whether viral pathogens contribute to the oncogenesis of rare skin cancers has not been systematically explored. Here, we analyzed 18 skin cancer types by exploiting off-target reads from commonly available next-generation sequencing data. We identified human papillomavirus 42 (HPV42) in all digital papillary adenocarcinoma (DPA) cases but not in any of 11,091 tumors from common cancer types. HPV42 was previously not described as an oncogenic driver, yet we show that HPV42 recapitulates the molecular hallmarks of oncogenic HPVs. Using a machine learning approach, we identified a conserved transcriptomic fingerprint of HPV transformation common to oncogenic HPVs, including HPV42. Collectively, our results establish HPV42 as an oncogenic HPV, which has implications for the diagnosis and treatment for DPA patients.

2022-10-18 | PXD031764 | Pride

Expression data from HPV(-) and HPV(+) squamous cell carcinoma cell lines

2010-12-01 | GSE24089 | GEO

Expression data from HPV(-) and HPV(+) squamous cell carcinoma cell lines

Project description:Oncogenic human papillomaviruses (HPVs) are associated with nearly all carcinomas of the uterine cervix and have also become an increasingly important factor in the etiology of a subset of oropharyngeal tumors. HPV-associated head and neck cancers (HNSCCs) have a distinct risk profile and appreciate a prognostic advantage compared to HPV-negative HNSCC. We analyzed the genome-wide expression patterns in two HPV(+) and two HPV(-) squamous cell carcinoma (SCC) cell lines. The Affymetrix Human Genome U133 Plus 2.0 Array platform was used to assess genome-wide expression differences between the HPV(+) and HPV(-) cell lines utilizing the RMA normalization package available for R. Cell lines analyzed: UM-SCC-4, UM-SCC-47, UM-SCC-74A, and CaSki.

2010-12-01 | E-GEOD-24089 | biostudies-arrayexpress

Gene Expression Profiles of HPV-Positive and -Negative Head/Neck and Cervical Cancers

Project description:Human papillomaviruses (HPVs) are associated with nearly all cervical cancers (CCs), 20-30% of head and neck cancers (HNCs), and other cancers. Because HNCs also arise in HPV-negative patients, this type of cancer provides unique opportunities to define similarities and differences of HPV-positive versus HPV-negative cancers arising in the same tissue. Here, we describe genome-wide expression profiling of 84 HNCs, CCs and site-matched normal epithelial samples in which we used laser capture microdissection to enrich samples for tumor-derived versus normal epithelial cells. This analysis revealed that HPV+HNCs and CCs differed in their patterns of gene expression yet shared many changes compared to HPV-HNCs. Some of these shared changes were predicted, but many others were not. Notably, HPV+HNCs and CCs were found to be upregulated in their expression of a distinct and larger subset of cell cycle genes than observed in HPV-HNC. Moreover, HPV+ cancers over-expressed testis-specific genes that are normally expressed only in meiotic cells. Many, though not all, of the hallmark differences between HPV+HNC and HPV-HNC were a direct consequence of HPV and in particular the viral E6 and E7 oncogenes. This included a novel association of HPV oncogenes with testes specific gene expression. These findings in primary human tumors provide novel biomarkers for early detection of HPV+ and HPV- cancers, and emphasize the potential value of targeting E6 and E7 function, alone or combined with radiation and/or traditional chemotherapy, in the treatment of HPV+ cancers. Keywords: Gene expression ptofiles of primary cancers

2007-05-15 | GSE6791 | GEO

Ecdysoneless protein regulates viral and cellular mRNA splicing to promote cervical oncogenesis

Project description:The high-risk subgroup of Human papilloma viruses (HPVs), exemplified by HPV16/18, are causally linked to human cancers of the anogenital tract, skin, and upper aerodigestive tract. The high-risk HPV oncoproteins E6 and E7 are expressed from a polycistronic transcript that can potentially give rise to alternatively spliced E6 mRNAs, a process important for E6 and E7 expression and oncogenic transformation. Previously, we identified ECD, the human homologue of the Drosophila ecdysoneless gene, as a novel HPV16 E6-interacting protein using Yeast two-hybrid system. Here, we show that the C-terminal region of ECD selectively binds to high-risk but not to low-risk HPV E6 proteins. We demonstrate that ECD is overexpressed in HPV+ as well as HPV- cervical and head and neck patient tumor samples. Using the TCGA dataset, we show that ECD mRNA overexpression predicts shorter survival in these cancer patients. Recent work from our laboratory showed that ECD associates with several components of RNA biogenesis/splicing machinery and are involved in mRNA export. Here, we show that ECD is an RNA binding protein and regulates mRNA splicing. RNAseq analyses of SiHa cells upon ECD knockdown (KD) revealed alterations of many cellular pathways with prominent downregulation of components of the mRNA splicing machinery. Further investigation revealed that ECD KD resulted in dysregulation of E6 RNA splicing, resulting in decreased E7 and increased RB protein. Furthermore, ECD KD dysregulated several cellular mRNAs known to be critical for HPV oncogenesis. Finally, we demonstrate that while ECD KD in cervical cancer cell lines led to a reduction in oncogenic traits, ECD overexpression together with E7 led to the immortalization of keratinocytes. Taken together, our results support a novel role of ECD in transcription and in viral and cellular mRNA splicing to support HPV-driven oncogenesis.

2022-06-01 | GSE174317 | GEO

Identification of downstream targets of the human papillomavirus E6 and E7 oncoproteins by RNA interference

Project description:Specific types of human papillomaviruses (HPVs) cause cervical cancer, the second most common tumor in females worldwide. Both cellular transformation and the maintenance of the oncogenic phenotype of HPV-positive tumor cells are linked to the expression of the viral E6 and E7 oncogenes. In order to identify downstream cellular target genes for the viral oncoproteins, we silenced endogenous E6 and E7 expression in HPV-positive HeLa cells by RNA interference (RNAi). Subsequently, we assessed changes of the cellular transcriptome by genome-wide microarray analysis. We identified, 648 genes wich were either downregulated (360 genes) or upregulated (288 genes) upon inhibition of E6/E7 expression. A large fraction of these genes is involved in tumour-relevant processes, such as apoptosis control, cell cycle regulation, or spindle formation. Others may represent novel cellular targets for the HPV oncogenes, such as a large group of C-MYC-associated genes involved in RNA splicing. Keywords: siRNA mediated knockdown

2007-07-01 | GSE6926 | GEO

The Hippo pathway transcription factors YAP and TAZ play HPV-type dependent roles in cervical cancer

Project description:Human papillomaviruses (HPVs) cause most cervical cancers and an increasing number of other anogenital and oral carcinomas, with most cases caused by HPV16 or HPV18. HPV hijacks host signalling pathways to promote proliferation, to drive carcinogenesis. Understanding these interactions could permit identification of much-needed therapeutics for HPV-driven malignancies. The Hippo signalling pathway is important in HPV+ cancers, with the downstream effector YAP playing a pro-oncogenic role. However, the significance of its paralogue TAZ remains largely uncharacterised in these cancers. We demonstrate that TAZ is dysregulated in a HPV-type dependent manner by a distinct mechanism to that of YAP and controls proliferation via alternative cellular targets. Analysis of cervical cancer cell lines and patient biopsies revealed that TAZ expression was only significantly increased in HPV18+ and HPV18-like cells and. TAZ knockdown reduced proliferation, migration, and invasion only in HPV18+ cells. RNA-sequencing of HPV18+ cervical cells revealed that YAP and TAZ have distinct targets, suggesting they promote different mechanisms. Thus, in HPV18+ cancers, YAP and TAZ play non-redundant roles. This analysis identified TOGARAM2 as a previously uncharacterised TAZ target and demonstrates its role as a key effector of TAZ-mediated proliferation, migration, and invasion in HPV18+ cancers.

2024-05-20 | GSE261673 | GEO

Genome-wide analysis of poly(I:C)-responsive gene expression by primary human keratinocytes with and without episomal human papillomavirus

Project description:Analysis of the effect of high-risk human papillomaviruses HPV16 and HPV18 in keratinocytes at gene expression level. The hypothesis tested in the present study was that HPVs inhibit the function of pathogen recognition receptors (PRRs), thereby evading the immune system. Results show that HPV-positive keratinocytes have a weaker response to poly(I:C), a synthetic double strand RNA agonist of viral PRRs, with IL1B as a central hub in a gene expression network of relative downregulation. Total RNA from eight primary undifferentiated keratinocyte cultures, four uninfected and four HPV-positive, that were either left unstimulated, or stimulated for 4 or 24 hrs with 25 ug/ml poly(I:C).

2011-03-14 | E-GEOD-21260 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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