Methyltransferase expression and tumor suppressor gene methylation in sporadic and familial colorectal cancer

Molecular mechanisms underlying coordinated hypermethylation of multiple CpG islands in cancer remain unclear and studies of methyltransferase enzymes have arrived at conflicting results. We focused on DNMT1 and DNMT3B, DNA methyltransferases responsible for (de novo) methylation, and EZH2, histone...

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Detalles Bibliográficos
Autores: Joensuu, Emmi I., Nieminen, Tania T., Lotsari, Johanna E., Pavicic, Walter Hernan, Abdel Rahman, Wael M., Peltomäki, Päivi
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2015
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/84663
Acceso en línea:http://hdl.handle.net/11336/84663
Access Level:acceso abierto
Palabra clave:METHYLTRANSFERASE
COLON CANCER
SPORADIC
FAMILIAL
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
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oai_identifier_str oai:ri.conicet.gov.ar:11336/84663
network_acronym_str AR
network_name_str Argentina
repository_id_str
dc.title.none.fl_str_mv Methyltransferase expression and tumor suppressor gene methylation in sporadic and familial colorectal cancer
title Methyltransferase expression and tumor suppressor gene methylation in sporadic and familial colorectal cancer
spellingShingle Methyltransferase expression and tumor suppressor gene methylation in sporadic and familial colorectal cancer
Joensuu, Emmi I.
METHYLTRANSFERASE
COLON CANCER
SPORADIC
FAMILIAL
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
title_short Methyltransferase expression and tumor suppressor gene methylation in sporadic and familial colorectal cancer
title_full Methyltransferase expression and tumor suppressor gene methylation in sporadic and familial colorectal cancer
title_fullStr Methyltransferase expression and tumor suppressor gene methylation in sporadic and familial colorectal cancer
title_full_unstemmed Methyltransferase expression and tumor suppressor gene methylation in sporadic and familial colorectal cancer
title_sort Methyltransferase expression and tumor suppressor gene methylation in sporadic and familial colorectal cancer
dc.creator.none.fl_str_mv Joensuu, Emmi I.
Nieminen, Tania T.
Lotsari, Johanna E.
Pavicic, Walter Hernan
Abdel Rahman, Wael M.
Peltomäki, Päivi
author Joensuu, Emmi I.
author_facet Joensuu, Emmi I.
Nieminen, Tania T.
Lotsari, Johanna E.
Pavicic, Walter Hernan
Abdel Rahman, Wael M.
Peltomäki, Päivi
author_role author
author2 Nieminen, Tania T.
Lotsari, Johanna E.
Pavicic, Walter Hernan
Abdel Rahman, Wael M.
Peltomäki, Päivi
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv METHYLTRANSFERASE
COLON CANCER
SPORADIC
FAMILIAL
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
topic METHYLTRANSFERASE
COLON CANCER
SPORADIC
FAMILIAL
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
description Molecular mechanisms underlying coordinated hypermethylation of multiple CpG islands in cancer remain unclear and studies of methyltransferase enzymes have arrived at conflicting results. We focused on DNMT1 and DNMT3B, DNA methyltransferases responsible for (de novo) methylation, and EZH2, histone (H3K27) methyltransferase, and examined their roles in tumor suppressor gene (TSG) methylation patterns we have previously established in sporadic and familial cancers. Our investigation comprised 165 tumors, stratified by tissue of origin (117 colorectal and 48 endometrial carcinomas) and sporadic vs. familial disease (57 sporadic vs. 60 familial, mainly Lynch syndrome, colorectal carcinomas). By immunohistochemical evaluation, EZH2 protein expression was associated with a TSG methylator phenotype. DNMT1, DNMT3B, and EZH2 were expressed at significantly higher levels in tumor vs. normal tissues. DNMT1 and EZH2 expression were positively correlated and higher in microsatellite-unstable vs. microsatellite-stable tumors, whether sporadic or hereditary. Ki-67 expression mirrored the same pattern. Promoter methylation of the methyltransferase genes themselves was addressed as a possible cause behind their altered expression. While DNMT1 or EZH2 did not show differential methylation between normal and tumor tissues, DNMT3B analysis corroborated the regulatory role of a distal promoter region. Our study shows that methyltransferase expression in cancer depends on the tissue of origin, microsatellite-instability status, cellular proliferation, and-in the case of DNMT3B-promoter methylation of the respective gene. Translation of methyltransferase expression into DNA methylation appears complex as suggested by the fact that except for EZH2, no clear association between methyltransferase protein expression and TSG methylation was observed.
publishDate 2015
dc.date.none.fl_str_mv 2015-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/84663
Joensuu, Emmi I.; Nieminen, Tania T.; Lotsari, Johanna E.; Pavicic, Walter Hernan; Abdel Rahman, Wael M.; et al.; Methyltransferase expression and tumor suppressor gene methylation in sporadic and familial colorectal cancer; Wiley-liss, Div John Wiley & Sons Inc; Genes, Chromosomes & Cancer.; 54; 12; 12-2015; 776-787
1045-2257
CONICET Digital
CONICET
url http://hdl.handle.net/11336/84663
identifier_str_mv Joensuu, Emmi I.; Nieminen, Tania T.; Lotsari, Johanna E.; Pavicic, Walter Hernan; Abdel Rahman, Wael M.; et al.; Methyltransferase expression and tumor suppressor gene methylation in sporadic and familial colorectal cancer; Wiley-liss, Div John Wiley & Sons Inc; Genes, Chromosomes & Cancer.; 54; 12; 12-2015; 776-787
1045-2257
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1002/gcc.22289
info:eu-repo/semantics/altIdentifier/doi/10.1002/gcc.22289
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley-liss, Div John Wiley & Sons Inc
publisher.none.fl_str_mv Wiley-liss, Div John Wiley & Sons Inc
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1799195429285396480
spelling Methyltransferase expression and tumor suppressor gene methylation in sporadic and familial colorectal cancerJoensuu, Emmi I.Nieminen, Tania T.Lotsari, Johanna E.Pavicic, Walter HernanAbdel Rahman, Wael M.Peltomäki, PäiviMETHYLTRANSFERASECOLON CANCERSPORADICFAMILIALhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Molecular mechanisms underlying coordinated hypermethylation of multiple CpG islands in cancer remain unclear and studies of methyltransferase enzymes have arrived at conflicting results. We focused on DNMT1 and DNMT3B, DNA methyltransferases responsible for (de novo) methylation, and EZH2, histone (H3K27) methyltransferase, and examined their roles in tumor suppressor gene (TSG) methylation patterns we have previously established in sporadic and familial cancers. Our investigation comprised 165 tumors, stratified by tissue of origin (117 colorectal and 48 endometrial carcinomas) and sporadic vs. familial disease (57 sporadic vs. 60 familial, mainly Lynch syndrome, colorectal carcinomas). By immunohistochemical evaluation, EZH2 protein expression was associated with a TSG methylator phenotype. DNMT1, DNMT3B, and EZH2 were expressed at significantly higher levels in tumor vs. normal tissues. DNMT1 and EZH2 expression were positively correlated and higher in microsatellite-unstable vs. microsatellite-stable tumors, whether sporadic or hereditary. Ki-67 expression mirrored the same pattern. Promoter methylation of the methyltransferase genes themselves was addressed as a possible cause behind their altered expression. While DNMT1 or EZH2 did not show differential methylation between normal and tumor tissues, DNMT3B analysis corroborated the regulatory role of a distal promoter region. Our study shows that methyltransferase expression in cancer depends on the tissue of origin, microsatellite-instability status, cellular proliferation, and-in the case of DNMT3B-promoter methylation of the respective gene. Translation of methyltransferase expression into DNA methylation appears complex as suggested by the fact that except for EZH2, no clear association between methyltransferase protein expression and TSG methylation was observed.Fil: Joensuu, Emmi I.. University of Helsinki; FinlandiaFil: Nieminen, Tania T.. University of Helsinki; FinlandiaFil: Lotsari, Johanna E.. University of Helsinki; FinlandiaFil: Pavicic, Walter Hernan. University of Helsinki; Finlandia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: Abdel Rahman, Wael M.. University of Helsinki; Finlandia. University of Sharjah; Emiratos Arabes UnidosFil: Peltomäki, Päivi. University of Helsinki; FinlandiaWiley-liss, Div John Wiley & Sons Inc2015-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/84663Joensuu, Emmi I.; Nieminen, Tania T.; Lotsari, Johanna E.; Pavicic, Walter Hernan; Abdel Rahman, Wael M.; et al.; Methyltransferase expression and tumor suppressor gene methylation in sporadic and familial colorectal cancer; Wiley-liss, Div John Wiley & Sons Inc; Genes, Chromosomes & Cancer.; 54; 12; 12-2015; 776-7871045-2257CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1002/gcc.22289info:eu-repo/semantics/altIdentifier/doi/10.1002/gcc.22289info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2024-05-08T13:52:14Zoai:ri.conicet.gov.ar:11336/84663instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982024-05-08 13:52:14.726CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
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