Molecular evidence of human papillomaviruses in the retinoblastoma tumor.
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ABSTRACT:
SUBMITTER: Javanmard D
PROVIDER: S-EPMC6863999 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:We use all the currently known 405 Papillomavirus (PV) sequences, 343 curated PV sequences from both humans and animals from the PAVE data base, to analyse the recombination dynamics of these viruses at the whole genome levels. After showing some evidence of human and non-human primate PV recombination, we report a comprehensive recombination analysis of all currently known 82 Alphapapillomaviruses (Alpha-PVs). We carried out an exploratory study and found novel recombination events between High-Risk HPV Types and Macaca fascicularis PV1 (MfPV1), Macaca Fuscata PV2 (MfuPV2) and Pan Paniscus PV1 (PpPV1) Papillomaviruses. This is the first evidence of interactions between PVs from different hosts and hence postulates the likelihood of ancient host switching among Alpha-PVs. Notwithstanding these results should be interpreted with caution because the major and minor parents indicated by RDP4 program are simply the sequences in the alignment that most closely resemble the actual parents. We found statistically significant differences between the phylogenies of the PV sequences with recombination regions and PV sequences without recombination regions using the Shimodaira-Hasegawa phylogenetic incongruence testing. We show that not more than 76MYA Alpha-PVs were in the same biological niche, a pre-requisite for recombination, and as the hosts evolved and diversified, the viruses adapted to specific host niches which eventually led to coevolution with specific hosts before speciation of primate species. Thus providing evidence that in ancient times no earlier than the Cretaceous period of the Mesozoic age, Alpha-PVs recombined and switched hosts, but whether this host switching is occurring currently is unknown. However, a clearer picture of the PVs evolutionary landscape can only be achieved with the incremental discovery of PV sequences, especially from the animal kingdom.
| S-EPMC7222169 | biostudies-literature
Project description:Bilateral retinoblastoma has served as a critical model for studying genetic predisposition to cancer, however international incidence of unilateral retinoblastoma is variable across populations suggesting the involvement of environmental factors. DNA from Human Papilloma Virus (HPV) has been found in human retinoblastoma tissue through polymerase chain reaction based methods in several independent reports. To search for HPV oncoproteins and characterize transcriptional profiles in retinoblastoma, we analyzed tumor tissue obtained after enucleation and cultured for one week from 13 previously untreated Mexican children with retinoblastoma. We identified the presence of E7 HPV oncoproteins using western blot analysis in HPV positive tumors, and using non-supervised methods of classification on gene expression microarrays data, tumors clustered according to the presence or absence of HPV DNA identified by PCR. These methods were unable to discriminate retinoblastoma tissues by laterality. 2,404 genes were differentially expressed between HPV positive and HPV negative retinoblastoma, including a group of genes involved in a transcriptional response to viral infection. This molecular evidence supports the hypothesis that HPV is involved in the molecular pathogenesis of these tumors.
2008-05-21 | GSE11488 | GEO
Project description:Bilateral retinoblastoma has served as a critical model for studying genetic predisposition to cancer, however international incidence of unilateral retinoblastoma is variable across populations suggesting the involvement of environmental factors. DNA from Human Papilloma Virus (HPV) has been found in human retinoblastoma tissue through polymerase chain reaction based methods in several independent reports. To search for HPV oncoproteins and characterize transcriptional profiles in retinoblastoma, we analyzed tumor tissue obtained after enucleation and cultured for one week from 13 previously untreated Mexican children with retinoblastoma. We identified the presence of E7 HPV oncoproteins using western blot analysis in HPV positive tumors, and using non-supervised methods of classification on gene expression microarrays data, tumors clustered according to the presence or absence of HPV DNA identified by PCR. These methods were unable to discriminate retinoblastoma tissues by laterality. 2,404 genes were differentially expressed between HPV positive and HPV negative retinoblastoma, including a group of genes involved in a transcriptional response to viral infection. This molecular evidence supports the hypothesis that HPV is involved in the molecular pathogenesis of these tumors. The 13 children and tumors examined here, are incident cases participating in a larger case-control study at two Pediatric Hospitals of third level of medical attention in Mexico City, that form part of the public health system. Nine different tumors positive and four negative to HPV by PCR were included in the experimental design. From these, seven are unilateral and six are bilateral and are considered biological replicas. Two unilateral and two bilateral cases were chosen to make technical replicas. From the surgical specimens, two tumor portions were obtained, one was frozen, DNA was extracted from it, and HPV status was assigned using MY09 and MY11 primers by PCR. Another portion of tumor tissue was used to grow in culture, separating viable cells from non viable cells through a ficoll gradient. In the eye, retinoblastoma usually grows into the vitreous which has no cells, and thus the tissue obtained is predominantly formed by tumor cells and few endothelial cells from capillaries in the tumor. Retinoblastoma grow in culture as non adherent cells, and when adherent cells were also present, cell suspension was moved to a new dish to keep retinoblastoma cells as the main or only cellular type as possible. We used a two channel platform with in house spotted microarrays. Since retinoblastoma has known classes: uni and bilateral, we sought to verify these classes or discover new, we used a class discovery approach and a reference experimental design. As the reference sample we used RNA form exponentially growing Saccharomyces cerevisiae because major signaling pathways and basic cellular processes among Saccharomyces cerevisiae and mammalian cells including cell cycle control and DNA repair mechanisms have a high degree of conservation. Also because yeast is easy to grow, and thus a reliable and robust source of reference RNA.
2008-05-20 | E-GEOD-11488 | biostudies-arrayexpress
Project description:Members of the Papillomaviridae family account for 27.9-30% of all infectious agents associated with human cancer. The aim of our study was to investigate the presence of high-risk HPV (human papilloma virus) genotypes in patients with periodontitis and a pronounced clinical picture. To achieve this goal, after proving the bacterial etiology of periodontitis, the samples positive for bacteria were examined for the presence of HPV. The genotype of HPV is also determined in samples with the presence of the virus proven by PCR (polymerase chain reaction). All positive tests for bacteria associated with the development of periodontitis indicated the presence of HPV. There was a statistically significant difference in HPV positive results between the periodontitis positive target group and the control group. The higher presence of high-risk HPV genotypes in the target group, which was also positive for the presence of periodontitis-causing bacteria, has been proven. A statistically significant relationship was established between the presence of periodontitis-causing bacteria and high-risk strains of HPV. The most common HPV genotype that tests positive for bacteria associated with the development of periodontitis is HPV58.
| S-EPMC10059129 | biostudies-literature
Project description:It is hypothesised that high risk for cancer human papillomaviruses (HPVs) have a causal role in prostate cancer. In 26 case control studies, high risk HPVs have been identified in benign and prostate cancers. High risk HPVs were identified in 325 (22.6%) of 1284 prostate cancers and in 113 (8.6%) of 1313 normal or benign prostate controls (p = 0.001). High risk HPVs of the same type have been identified in both normal and benign prostate tissues prior to the development of HPV positive prostate cancer. High risk HPVs can be associated with inflammatory prostatitis leading to benign prostate hyperplasia and later prostate cancer. Normal human prostate epithelial cells can be immortalised by experimental exposure to HPVs. HPVs are probably sexually transmitted. The role of HPVs in prostate cancer is complex and differs from HPVs associated cervical cancer. HPV infections may initiate prostate oncogenesis directly and influence oncogenesis indirectly via APOBEC enzymes. HPVs may collaborate with other pathogens in prostate oncogenesis. Although HPVs are only one of many pathogens that have been identified in prostate cancer, they are the only infectious pathogen which can be prevented by vaccination. A causal role for HPVs in prostate cancer is highly likely.
| S-EPMC7359253 | biostudies-literature
Project description:The expression of the human papillomavirus (HPV) E6/E7 oncogenes is crucial for HPV-induced malignant cell transformation. The identification of cellular targets attacked by the HPV oncogenes is critical for our understanding of the molecular mechanisms of HPV-associated carcinogenesis and may open novel therapeutic opportunities. Here, we identify the Lens Epithelial-Derived Growth Factor (LEDGF) gene as a novel cellular target gene for the HPV oncogenes. Elevated LEDGF expression has been recently linked to human carcinogenesis and can protect tumor cells towards different forms of cellular stress. We show that intracellular LEDGF mRNA and protein levels in HPV-positive cancer cells are critically dependent on the maintenance of viral oncogene expression. Ectopic E6/E7 expression stimulates LEDGF transcription in primary keratinocytes, at least in part via activation of the LEDGF promoter. Repression of endogenous LEDGF expression by RNA interference results in an increased sensitivity of HPV-positive cancer cells towards genotoxic agents. Immunohistochemical analyses of cervical tissue specimens reveal a highly significant increase of LEDGF protein levels in HPV-positive lesions compared to histologically normal cervical epithelium. Taken together, these results indicate that the E6/E7-dependent maintenance of intracellular LEDGF expression is critical for protecting HPV-positive cancer cells against various forms of cellular stress, including DNA damage. This could support tumor cell survival and contribute to the therapeutic resistance of cervical cancers towards genotoxic treatment strategies in the clinic.
| S-EPMC3946365 | biostudies-literature
Project description:Molecular evidence and gene expression profiles implicating involvement of Human Papilloma Virus in human retinoblastoma
| PRJNA106417 | ENA
Project description:Retinoblastoma (RB; encoded by RB1) is a tumor suppressor that is frequently disrupted in tumorigenesis and acts in multiple cell types to suppress cell cycle progression. The role of RB in tumor progression, however, is poorly defined. Here, we have identified a critical role for RB in protecting against tumor progression through regulation of targets distinct from cell cycle control. In analyses of human prostate cancer samples, RB loss was infrequently observed in primary disease and was predominantly associated with transition to the incurable, castration-resistant state. Further analyses revealed that loss of the RB1 locus may be a major mechanism of RB disruption and that loss of RB function was associated with poor clinical outcome. Modeling of RB dysfunction in vitro and in vivo revealed that RB controlled nuclear receptor networks critical for tumor progression and that it did so via E2F transcription factor 1-mediated regulation of androgen receptor (AR) expression and output. Through this pathway, RB depletion induced unchecked AR activity that underpinned therapeutic bypass and tumor progression. In agreement with these findings, disruption of the RB/E2F/nuclear receptor axis was frequently observed in the transition to therapy resistance in human disease. Together, these data reveal what we believe to be a new paradigm for RB function in controlling prostate tumor progression and lethal tumor phenotypes.
| S-EPMC2993601 | biostudies-literature
Project description:Retinoblastoma (RB) is the most common eye cancer in children that has a high mortality rate when left untreated. Mouse models for retinoblastoma have been established but are time- and cost-intensive. The aim of this work was to evaluate an orthotopic transplantation model of retinoblastoma in zebrafish that also allows for tracking migratory routes and to explore advantages and disadvantages with respect to drug testing. Three fluorescence-labeled retinoblastoma cell lines (RB355, WERI-RB-1, Y79) were injected into the left eye of two-day-old zebrafish, while the un-injected right eye served as control. The migratory trajectories of injected retinoblastoma cells were observed until 8 days post injection (dpi), both in lateral and dorsal view, and measuring fluorescence intensity of injected cells was done for RB355 cells. Time until the onset of migration and routes for all three retinoblastoma cell lines were comparable and resulted in migration into the brain and ventricles of the forebrain, midbrain and hindbrain. Involvement of the optic nerve was observed in 10% of injections with the RB355 cell line, 15% with Y79 cells and 5% with WERI-RB-1 cells. Fluorescence intensity of injected RB355 cells showed an initial increase until five dpi, but then decreased with high variability until the end of observation. The zebrafish eye is well suited for the analysis of migratory routes in retinoblastoma and closely mirrors patterns of retinoblastoma metastases in humans.
| S-EPMC9736091 | biostudies-literature
Project description:Typing of human papillomaviruses (HPV) by DNA hybridization procedures, such as reverse line blot (RLB) assay, is sensitive and well validated. However, the application of these assays to high-throughput analyses is limited. Here, we describe the development of multiplex human papillomavirus genotyping (MPG), a quantitative and sensitive high-throughput procedure for the identification of multiple high- and low-risk genital HPV genotypes in a single reaction. MPG is based on the amplification of HPV DNA by a general primer PCR (GP5+/6+) and the subsequent detection of the products with type-specific oligonucleotide probes coupled to fluorescence-labeled polystyrene beads (Luminex suspension array technology). Up to 100 different HPV types can be detected simultaneously with MPG, and the method is fast and labor saving. We detected all 22 HPV types examined with high specificity and reproducibility (the median interplate coefficient of variation was below 10%). Detection limits for the different HPV types varied between 100 and 800 pg of PCR products. We compared the performance of MPG to an established RLB assay on GP5+/6+-PCR products derived from 94 clinical samples. The evaluation showed an excellent agreement (kappa = 0.922) but also indicated a higher sensitivity of MPG. In conclusion, MPG appears to be highly suitable for large-scale epidemiological studies and vaccination trials as well as for routine diagnostic purposes.
| S-EPMC1392679 | biostudies-literature