Molecular analysis of cellular loci disrupted by papillomavirus 16 integration in cervical cancer: Frequent viral integration in topologically destabilized and transcriptionally active chromosomal regions

1996 ◽  
Vol 49 (1) ◽  
pp. 15-22 ◽  
Author(s):  
Kong-Bung Choo ◽  
Chuan-Mu Chen ◽  
Chih-Ping Han ◽  
Winston T.K. Cheng ◽  
Lo-Chun Au
Keyword(s):  
Cervical Cancer ◽  
Molecular Analysis ◽  
Viral Integration

The role of viral integration in the development of cervical cancer

2005 ◽  
Vol 158 (1) ◽  
pp. 27-34 ◽  
Author(s):  
Tingxi Yu ◽  
Matthew J. Ferber ◽  
Tak Hong Cheung ◽  
Tong Kwok Hung Chung ◽  
Yick Fu Wong ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Viral Integration

scholarly journals Utilization of a cell-penetrating peptide-adaptor for delivery of HPV protein E2 into cervical cancer cells to arrest cell growth and promote cell death

2020 ◽  
Author(s):  
Julia C. LeCher ◽  
Hope L. Didier ◽  
Robert L. Dickson ◽  
Lauren R. Slaughter ◽  
Juana C. Bejarano ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Cell Penetrating Peptides ◽  
Viral Integration ◽  
E2 Protein ◽  
Cell Penetrating ◽  
Cervical Cancer Cells ◽  
E6 And E7

AbstractCervical cancer is the second leading cause of cancer deaths in women worldwide. Human papillomavirus (HPV) is the causative agent of nearly all forms of cervical cancer, which arises upon viral integration into the host genome and concurrent loss of regulatory gene E2. E2 protein regulates viral oncoproteins E6 and E7. Loss of E2 upon viral integration results in unregulated expression and activity of E6 and E7, which promotes carcinogenesis. Previous studies using gene-based delivery show that reintroduction of E2 into cervical cancer cell lines can reduce proliferative capacity and promote apoptosis. However, owing in part to limitations on transfection in vivo, E2 reintroduction has yet to achieve therapeutic usefulness. A promising new approach is protein-based delivery systems utilizing cell-penetrating peptides (CPPs). CPPs readily traverse the plasma membrane and are able to carry with them biomolecular ‘cargos’ to which they are attached. Though more than two decades of research have been dedicated to their development for delivery of biomolecular therapeutics, the full potential of CPPs has yet to be realized as the field is hindered by the tendency of CPP-linked cargos to be trapped in endosomes as well as having significant off-target potential in vivo. Using a CPP-adaptor system that reversibly binds cargo thereby overcoming the endosomal entrapment that hampers other CPP methods, bioactive E2 protein was delivered into living cervical cancer cells, resulting in inhibition of cellular proliferation and promotion of cell death in a time- and dose-dependent manner. The results suggest that this nucleic acid- and virus-free delivery method could be harnessed to develop novel, effective protein therapeutics for treatment of cervical cancer.

scholarly journals ViFi: accurate detection of viral integration and mRNA fusion reveals indiscriminate and unregulated transcription in proximal genomic regions in cervical cancer

2018 ◽  
Vol 46 (7) ◽  
pp. 3309-3325 ◽  
Author(s):  
Nam-phuong D Nguyen ◽  
Viraj Deshpande ◽  
Jens Luebeck ◽  
Paul S Mischel ◽  
Vineet Bafna
Keyword(s):  
Cervical Cancer ◽  
Viral Integration ◽  
Accurate Detection ◽  
Genomic Regions

Molecular analysis of growth regulatory functions of papillomavirus oncogenes E6 and E7 in cervical cancer cells

1995 ◽  
Vol 121 (S1) ◽  
pp. S25-S25
Author(s):  
M. von Knebel Doeberitz ◽  
F. Aengeneyndt ◽  
U. Schäfer ◽  
P. Jansen-Dürr ◽  
D. Spitkovsky
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Molecular Analysis ◽  
Cervical Cancer Cells ◽  
E6 And E7 ◽  
Regulatory Functions

scholarly journals Human papilloma virus (HPV) integration signature in Cervical Cancer: identification of MACROD2 gene as HPV hot spot integration site

2020 ◽  
Author(s):  
Maud Kamal ◽  
◽  
Sonia Lameiras ◽  
Marc Deloger ◽  
Adeline Morel ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Human Papilloma Virus ◽  
Integration Site ◽  
Hot Spot ◽  
Chromosome Instability ◽  
Anal Carcinoma ◽  
Viral Integration ◽  
Papilloma Virus ◽  
Molecular Features ◽  
Next Generation Sequencing Ngs

Abstract Background Cervical cancer (CC) remains a leading cause of gynaecological cancer-related mortality with infection by human papilloma virus (HPV) being the most important risk factor. We analysed the association between different viral integration signatures, clinical parameters and outcome in pre-treated CCs. Methods Different integration signatures were identified using HPV double capture followed by next-generation sequencing (NGS) in 272 CC patients from the BioRAIDs study [NCT02428842]. Correlations between HPV integration signatures and clinical, biological and molecular features were assessed. Results Episomal HPV was much less frequent in CC as compared to anal carcinoma (p < 0.0001). We identified >300 different HPV-chromosomal junctions (inter- or intra-genic). The most frequent integration site in CC was in MACROD2 gene followed by MIPOL1/TTC6 and TP63. HPV integration signatures were not associated with histological subtype, FIGO staging, treatment or PFS. HPVs were more frequently episomal in PIK3CA mutated tumours (p = 0.023). Viral integration type was dependent on HPV genotype (p < 0.0001); HPV18 and HPV45 being always integrated. High HPV copy number was associated with longer PFS (p = 0.011). Conclusions This is to our knowledge the first study assessing the prognostic value of HPV integration in a prospectively annotated CC cohort, which detects a hotspot of HPV integration at MACROD2; involved in impaired PARP1 activity and chromosome instability.

scholarly journals Impact of viral and host DNA methylations on HPV16-related cervical cancer pathogenesis

Tumor Biology ◽  
2017 ◽  
Vol 39 (5) ◽  
pp. 101042831769979 ◽  
Author(s):  
Shrinka Sen ◽  
Paramita Mandal ◽  
Amrapali Bhattacharya ◽  
Sudip Kundu ◽  
Rahul Roy Chowdhury ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Dna Methyltransferases ◽  
Viral Integration ◽  
Dna Hypomethylation ◽  
Significant Linear Trend ◽  
Hpv16 E6 ◽  
Cpg Motifs ◽  
Cancer Pathogenesis ◽  
Episomal Hpv16 ◽  
Negative Controls

Epigenetic alterations within human papillomavirus (HPV) and host cellular genomes are known to occur during cervical carcinogenesis. Our objective was to analyse the influence of (1) methylation within two immunostimulatory CpG motifs within HPV16 E6 and E7 genes around the viral late promoter and their correlation, if any, with expression deregulation of host receptor (TLR9) and DNA methyltransferases (DNMT1, DNMT3A and DNMT3B) and (2) global DNA methylation levels within CpGs of the repetitive Alu sequences, on cervical cancer (CaCx) pathogenesis. Significantly higher proportions of CaCx samples portrayed methylation in immunostimulatory CpG motifs, compared to HPV16-positive non-malignant samples, with cases harbouring episomal HPV16 showing decreased methylation compared to those with viral integration. A significant linear trend of TLR9 upregulation was recorded in the order of HPV–negative controls < HPV16-positive non-malignant samples < HPV16-positive CaCx cases. TLR9 upregulation in cases with episomal HPV16 was again higher among those with non-methylated immunostimulatory CpG motifs. Comparison of cases with HPV–negative controls revealed that DNMT3A was significantly downregulated only among integrated cases, DNMT3B was significantly overexpressed among both categories of cases, although at variable levels, while DNMT1 failed to show any deregulated expression among the cases. Global host DNA hypomethylation, also showed a significant linear increasing trend through the progressive CaCx development stages mentioned above and was most prominently higher among cases with episomal HPV16 as opposed to viral integration. Thus, HPV16 and host methylations appear to influence CaCx pathogenesis, with differential molecular signatures among CaCx cases with episomal and integrated HPV16.

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