H19-DMR allele-specific methylation analysis reveals epigenetic heterogeneity of CTCF binding site 6 but not of site 5 in head-and-neck carcinomas: A pilot case-control analysis
Autor(a) principal: | |
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Data de Publicação: | 2006 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://hdl.handle.net/11449/224725 |
Resumo: | Aberrant methylation of seven potential binding sites of the CTCF factor in the differentially methylated region upstream of the H19 gene (H19-DMR) has been suggested as critical for the regulation of IGF2 and H19 imprinted genes. In this study, we analyzed the allele-specific methylation pattern of CTCF binding sites 5 and 6 using methylation-sensitive restriction enzyme PCR followed by RFLP analysis in matched tumoral and lymphocyte DNA from head-and-neck squamous cell carcinoma (HNSCC) patients, as well as in lymphocyte DNA from control individuals who were cancer-free. The monoallelic methylation pattern was maintained in CTCF binding site 5 in 22 heterozygous out of 91 samples analyzed. Nevertheless, a biallelic methylation pattern was detected in CTCF binding site 6 in a subgroup of HNSCC patients as a somatic acquired feature of tumor cells. An atypical biallelic methylation was also observed in both tumor and lymphocyte DNA from two patients, and at a high frequency in the control group (29 out of 64 informative controls). Additionally, we found that the C/T transition detected by HhaI RFLP suppressed one dinucleotide CpG in critical CTCF binding site 6, of a mutation showing polymorphic frequencies. Although a heterogeneous methylation pattern was observed after DNA sequencing modified by sodium bisulfite, the biallelic methylation pattern was confirmed in 9 out of 10 HNSCCs. These findings are likely to be relevant in the epigenetic regulation of the DMR, especially in pathological conditions in which the imprinting of IGF2 and H19 genes is disrupted. |
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H19-DMR allele-specific methylation analysis reveals epigenetic heterogeneity of CTCF binding site 6 but not of site 5 in head-and-neck carcinomas: A pilot case-control analysisDifferentially methylated regionGenomic imprintingH19 geneHead-and-neck carcinomasPolymorphismAberrant methylation of seven potential binding sites of the CTCF factor in the differentially methylated region upstream of the H19 gene (H19-DMR) has been suggested as critical for the regulation of IGF2 and H19 imprinted genes. In this study, we analyzed the allele-specific methylation pattern of CTCF binding sites 5 and 6 using methylation-sensitive restriction enzyme PCR followed by RFLP analysis in matched tumoral and lymphocyte DNA from head-and-neck squamous cell carcinoma (HNSCC) patients, as well as in lymphocyte DNA from control individuals who were cancer-free. The monoallelic methylation pattern was maintained in CTCF binding site 5 in 22 heterozygous out of 91 samples analyzed. Nevertheless, a biallelic methylation pattern was detected in CTCF binding site 6 in a subgroup of HNSCC patients as a somatic acquired feature of tumor cells. An atypical biallelic methylation was also observed in both tumor and lymphocyte DNA from two patients, and at a high frequency in the control group (29 out of 64 informative controls). Additionally, we found that the C/T transition detected by HhaI RFLP suppressed one dinucleotide CpG in critical CTCF binding site 6, of a mutation showing polymorphic frequencies. Although a heterogeneous methylation pattern was observed after DNA sequencing modified by sodium bisulfite, the biallelic methylation pattern was confirmed in 9 out of 10 HNSCCs. These findings are likely to be relevant in the epigenetic regulation of the DMR, especially in pathological conditions in which the imprinting of IGF2 and H19 genes is disrupted.Department of Genetics Institute of Biosciences UNESP, Botucatu, SP 18618-000Department of Urology Faculty of Medicine UNESP, Botucatu, SP 18618-000Department of Head and Neck Surgery Amaral Carvalho Hospital, Jau, SP 17210-080Department of Head and Neck Surgery and Otorhinolaryngology A.C. Camargo Hospital, Sao Paulo, SP 01509-010Department of Genetics Institute of Biosciences UNESP, Botucatu, SP 18618-000Department of Urology Faculty of Medicine UNESP, Botucatu, SP 18618-000Universidade Estadual Paulista (UNESP)Amaral Carvalho HospitalA.C. Camargo HospitalEsteves, Leda Isabel De Castro Valente [UNESP]Cervigne, Nilva De Karla [UNESP]Javaroni, Afonso Do CarmoMagrin, JoséKowalski, Luiz PauloRainho, Cláudia Aparecida [UNESP]Rogatto, Silvia Regina [UNESP]2022-04-28T20:07:37Z2022-04-28T20:07:37Z2006-02-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article397-404International Journal of Molecular Medicine, v. 17, n. 2, p. 397-404, 2006.1107-37561791-244Xhttp://hdl.handle.net/11449/2247252-s2.0-33644858912Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengInternational Journal of Molecular Medicineinfo:eu-repo/semantics/openAccess2022-04-28T20:07:37Zoai:repositorio.unesp.br:11449/224725Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462022-04-28T20:07:37Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
H19-DMR allele-specific methylation analysis reveals epigenetic heterogeneity of CTCF binding site 6 but not of site 5 in head-and-neck carcinomas: A pilot case-control analysis |
title |
H19-DMR allele-specific methylation analysis reveals epigenetic heterogeneity of CTCF binding site 6 but not of site 5 in head-and-neck carcinomas: A pilot case-control analysis |
spellingShingle |
H19-DMR allele-specific methylation analysis reveals epigenetic heterogeneity of CTCF binding site 6 but not of site 5 in head-and-neck carcinomas: A pilot case-control analysis Esteves, Leda Isabel De Castro Valente [UNESP] Differentially methylated region Genomic imprinting H19 gene Head-and-neck carcinomas Polymorphism |
title_short |
H19-DMR allele-specific methylation analysis reveals epigenetic heterogeneity of CTCF binding site 6 but not of site 5 in head-and-neck carcinomas: A pilot case-control analysis |
title_full |
H19-DMR allele-specific methylation analysis reveals epigenetic heterogeneity of CTCF binding site 6 but not of site 5 in head-and-neck carcinomas: A pilot case-control analysis |
title_fullStr |
H19-DMR allele-specific methylation analysis reveals epigenetic heterogeneity of CTCF binding site 6 but not of site 5 in head-and-neck carcinomas: A pilot case-control analysis |
title_full_unstemmed |
H19-DMR allele-specific methylation analysis reveals epigenetic heterogeneity of CTCF binding site 6 but not of site 5 in head-and-neck carcinomas: A pilot case-control analysis |
title_sort |
H19-DMR allele-specific methylation analysis reveals epigenetic heterogeneity of CTCF binding site 6 but not of site 5 in head-and-neck carcinomas: A pilot case-control analysis |
author |
Esteves, Leda Isabel De Castro Valente [UNESP] |
author_facet |
Esteves, Leda Isabel De Castro Valente [UNESP] Cervigne, Nilva De Karla [UNESP] Javaroni, Afonso Do Carmo Magrin, José Kowalski, Luiz Paulo Rainho, Cláudia Aparecida [UNESP] Rogatto, Silvia Regina [UNESP] |
author_role |
author |
author2 |
Cervigne, Nilva De Karla [UNESP] Javaroni, Afonso Do Carmo Magrin, José Kowalski, Luiz Paulo Rainho, Cláudia Aparecida [UNESP] Rogatto, Silvia Regina [UNESP] |
author2_role |
author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (UNESP) Amaral Carvalho Hospital A.C. Camargo Hospital |
dc.contributor.author.fl_str_mv |
Esteves, Leda Isabel De Castro Valente [UNESP] Cervigne, Nilva De Karla [UNESP] Javaroni, Afonso Do Carmo Magrin, José Kowalski, Luiz Paulo Rainho, Cláudia Aparecida [UNESP] Rogatto, Silvia Regina [UNESP] |
dc.subject.por.fl_str_mv |
Differentially methylated region Genomic imprinting H19 gene Head-and-neck carcinomas Polymorphism |
topic |
Differentially methylated region Genomic imprinting H19 gene Head-and-neck carcinomas Polymorphism |
description |
Aberrant methylation of seven potential binding sites of the CTCF factor in the differentially methylated region upstream of the H19 gene (H19-DMR) has been suggested as critical for the regulation of IGF2 and H19 imprinted genes. In this study, we analyzed the allele-specific methylation pattern of CTCF binding sites 5 and 6 using methylation-sensitive restriction enzyme PCR followed by RFLP analysis in matched tumoral and lymphocyte DNA from head-and-neck squamous cell carcinoma (HNSCC) patients, as well as in lymphocyte DNA from control individuals who were cancer-free. The monoallelic methylation pattern was maintained in CTCF binding site 5 in 22 heterozygous out of 91 samples analyzed. Nevertheless, a biallelic methylation pattern was detected in CTCF binding site 6 in a subgroup of HNSCC patients as a somatic acquired feature of tumor cells. An atypical biallelic methylation was also observed in both tumor and lymphocyte DNA from two patients, and at a high frequency in the control group (29 out of 64 informative controls). Additionally, we found that the C/T transition detected by HhaI RFLP suppressed one dinucleotide CpG in critical CTCF binding site 6, of a mutation showing polymorphic frequencies. Although a heterogeneous methylation pattern was observed after DNA sequencing modified by sodium bisulfite, the biallelic methylation pattern was confirmed in 9 out of 10 HNSCCs. These findings are likely to be relevant in the epigenetic regulation of the DMR, especially in pathological conditions in which the imprinting of IGF2 and H19 genes is disrupted. |
publishDate |
2006 |
dc.date.none.fl_str_mv |
2006-02-01 2022-04-28T20:07:37Z 2022-04-28T20:07:37Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
International Journal of Molecular Medicine, v. 17, n. 2, p. 397-404, 2006. 1107-3756 1791-244X http://hdl.handle.net/11449/224725 2-s2.0-33644858912 |
identifier_str_mv |
International Journal of Molecular Medicine, v. 17, n. 2, p. 397-404, 2006. 1107-3756 1791-244X 2-s2.0-33644858912 |
url |
http://hdl.handle.net/11449/224725 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
International Journal of Molecular Medicine |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
397-404 |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1803047338775674880 |