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Methylation of human papillomavirus type 16 CpG sites at E2-binding site 1 (E2BS1), E2BS2, and the Sp1-binding site in cervical cancer samples as determined by high-resolution melting analysis-PCR

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dc.creatorJacquin, Elisespa
dc.creatorBaraquin, Alicespa
dc.creatorRamanah, Rajeevspa
dc.creatorCarcopino, Xavierspa
dc.creatorMorel, Adrien
dc.creatorValmary-Degano, Séverinespa
dc.creatorBravo, Ignacio G.spa
dc.creatorde Sanjosé, Silviaspa
dc.creatorRiethmuller, Didierspa
dc.creatorMougin, Christianespa
dc.creatorPrétet, Jean-Lucspa
dc.date.accessioned2020-08-19T14:45:58Z
dc.date.available2020-08-19T14:45:58Z
dc.date.created2013-09-20spa
dc.description.abstractHigh-risk (HR) human papillomavirus (HPV)-associated carcinogenesis is driven mainly by the overexpression of E7 and E6 oncoproteins following viral DNA integration and the concomitant loss of the E2 open reading frame (ORF). However, the integration of HR-HPV DNA is not systematically observed in cervical cancers. The E2 protein acts as a transcription factor that governs viral oncogene expression. The methylation of CpGs in the E2-binding sites (E2BSs) in the viral long control region abrogates E2 binding, thus impairing the E2-mediated regulation of E7/E6 transcription. Here, high-resolution melting (HRM)–PCR was developed to quantitatively analyze the methylation statuses of E2BS1, E2BS2, and the specificity protein 1 (Sp1)-binding site in 119 HPV16-positive cervical smears. This is a rapid assay that is suitable for the analysis of cervical samples. The proportion of cancer samples with methylated E2BS1, E2BS2, and Sp1-binding site CpGs was 47%, whereas the vast majority of samples diagnosed as being within normal limits, low-grade squamous intraepithelial lesions (LSIL), or high-grade squamous intraepithelial lesions (HSIL) harbored unmethylated CpGs. Methylation levels varied widely, since some cancer samples harbored up to 60% of methylated HPV16 genomes. A pyrosequencing approach was used as a confirmation test and highlighted that quantitative measurement of methylation can be achieved by HRM-PCR. Its prognostic value deserves to be investigated alone or in association with other biomarkers. The reliability of this single-tube assay offers great opportunities for the investigation of HPV16 methylation in other HPV-related cancers, such as head and neck cancers, which are a major public health burden.eng
dc.format.mimetypeapplication/pdf
dc.identifier.doihttps://doi.org/10.1128/JCM.01106-13
dc.identifier.issnISSN: 0095-1137
dc.identifier.issnEISSN: 1098-660X
dc.identifier.urihttps://repository.urosario.edu.co/handle/10336/28129
dc.language.isoengspa
dc.publisherAmerican Society for Microbiologyspa
dc.relation.citationTitleJournal of Clinical Microbiology
dc.relation.ispartofJournal of Clinical Microbiology, ISSN: 0095-1137;EISSN: 1098-660X, Vol., No.(); pp. spa
dc.relation.urihttps://jcm.asm.org/content/jcm/51/10/3207.full.pdfspa
dc.rights.accesRightsinfo:eu-repo/semantics/openAccess
dc.rights.accesoAbierto (Texto Completo)spa
dc.sourceJournal of Clinical Microbiologyspa
dc.source.instnameinstname:Universidad del Rosario
dc.source.reponamereponame:Repositorio Institucional EdocUR
dc.subject.keywordDNAspa
dc.subject.keywordViral geneticsspa
dc.subject.keywordDNAspa
dc.subject.keywordviral metabolismspa
dc.subject.keywordDNA-binding proteins metabolismspa
dc.subject.keywordHuman papillomavirus 16 geneticsspa
dc.subject.keywordOncogene proteinsspa
dc.subject.keywordViral metabolismspa
dc.subject.keywordUterine cervical neoplasms virologyspa
dc.subject.keywordFemalespa
dc.titleMethylation of human papillomavirus type 16 CpG sites at E2-binding site 1 (E2BS1), E2BS2, and the Sp1-binding site in cervical cancer samples as determined by high-resolution melting analysis-PCRspa
dc.title.TranslatedTitleMetilación de sitios CpG del virus del papiloma humano tipo 16 en el sitio de unión 1 de E2 (E2BS1), E2BS2 y el sitio de unión de Sp1 en muestras de cáncer de cuello uterino, según lo determinado por análisis de fusión de alta resolución-PCRspa
dc.typearticleeng
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersion
dc.type.spaArtículospa
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