DNA methylation index and methylation profile of invasive ductal breast tumors

Autores
Marzese, Diego Matías; Hoon, Dave S.B.; Chong, Kelly K.; Gago, Francisco E.; Orozco, Javier Dario; Tello, Olga M.; Vargas Roig, Laura Maria; Roque Moreno, Maria
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Breast carcinogenesis is a multistep process that involves both genetic and epigenetic alterations. Identification of aberrantly methylated genes in breast tumors and their relation to clinical parameters can contribute to improved diagnostic, prognostic, and therapeutic decision making. Our objective in the present study was to identify the methylation status of 34 cancer-involved genes in invasive ductal carcinomas (IDC). Each of the 70 IDC cases analyzed had a unique methylation profile. The highest methylation frequency was detected in the WT1 (95.7%) and RASSF1 (71.4%) genes. Hierarchical cluster analysis revealed three clusters with different distribution of the prognostic factors tumor grade, lymph node metastasis, and proliferation rate. Methylation of TP73 was associated with high histological grade and high proliferation rate; methylation of RARB was associated with lymph node metastasis. Concurrent methylation of TP73 and RARB was associated with high histological grade, high proliferation rate, increased tumor size, and lymph node metastasis. Patients with more than six methylated genes had higher rates of relapse events and cancer deaths. In multivariate analysis, TP73 methylation and the methylation index were associated with disease outcome. Our results indicate that methylation index and methylation of TP73 and/or RARB are related to unfavorable prognostic factors in patients with IDC. These epigenetic markers should be validated in further studies to improve breast cancer management. © 2012 American Society for Investigative Pathology and the Association for Molecular Pathology.
Fil: Marzese, Diego Matías. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina. Universidad Nacional de Cuyo; Argentina
Fil: Hoon, Dave S.B.. Saint John's Health Center; Estados Unidos
Fil: Chong, Kelly K.. Saint John's Health Center; Estados Unidos
Fil: Gago, Francisco E.. Universidad Nacional de Cuyo; Argentina. Centro Médico de Mendoza; Argentina
Fil: Orozco, Javier Dario. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Cuyo; Argentina. Centro Médico de Mendoza; Argentina
Fil: Tello, Olga M.. Universidad Nacional de Cuyo; Argentina
Fil: Vargas Roig, Laura Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo; Argentina
Fil: Roque Moreno, Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina. Universidad Nacional de Cuyo; Argentina
Materia
Methylation Index
Retinoic Acid Receptor Beta
Tumor Protein P73
Breast Cancer
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/71523

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repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling DNA methylation index and methylation profile of invasive ductal breast tumorsMarzese, Diego MatíasHoon, Dave S.B.Chong, Kelly K.Gago, Francisco E.Orozco, Javier DarioTello, Olga M.Vargas Roig, Laura MariaRoque Moreno, MariaMethylation IndexRetinoic Acid Receptor BetaTumor Protein P73Breast Cancerhttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Breast carcinogenesis is a multistep process that involves both genetic and epigenetic alterations. Identification of aberrantly methylated genes in breast tumors and their relation to clinical parameters can contribute to improved diagnostic, prognostic, and therapeutic decision making. Our objective in the present study was to identify the methylation status of 34 cancer-involved genes in invasive ductal carcinomas (IDC). Each of the 70 IDC cases analyzed had a unique methylation profile. The highest methylation frequency was detected in the WT1 (95.7%) and RASSF1 (71.4%) genes. Hierarchical cluster analysis revealed three clusters with different distribution of the prognostic factors tumor grade, lymph node metastasis, and proliferation rate. Methylation of TP73 was associated with high histological grade and high proliferation rate; methylation of RARB was associated with lymph node metastasis. Concurrent methylation of TP73 and RARB was associated with high histological grade, high proliferation rate, increased tumor size, and lymph node metastasis. Patients with more than six methylated genes had higher rates of relapse events and cancer deaths. In multivariate analysis, TP73 methylation and the methylation index were associated with disease outcome. Our results indicate that methylation index and methylation of TP73 and/or RARB are related to unfavorable prognostic factors in patients with IDC. These epigenetic markers should be validated in further studies to improve breast cancer management. © 2012 American Society for Investigative Pathology and the Association for Molecular Pathology.Fil: Marzese, Diego Matías. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina. Universidad Nacional de Cuyo; ArgentinaFil: Hoon, Dave S.B.. Saint John's Health Center; Estados UnidosFil: Chong, Kelly K.. Saint John's Health Center; Estados UnidosFil: Gago, Francisco E.. Universidad Nacional de Cuyo; Argentina. Centro Médico de Mendoza; ArgentinaFil: Orozco, Javier Dario. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Cuyo; Argentina. Centro Médico de Mendoza; ArgentinaFil: Tello, Olga M.. Universidad Nacional de Cuyo; ArgentinaFil: Vargas Roig, Laura Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo; ArgentinaFil: Roque Moreno, Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina. Universidad Nacional de Cuyo; ArgentinaAmerican Society of Investigative Pathology2012-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/71523Marzese, Diego Matías; Hoon, Dave S.B.; Chong, Kelly K.; Gago, Francisco E.; Orozco, Javier Dario; et al.; DNA methylation index and methylation profile of invasive ductal breast tumors; American Society of Investigative Pathology; Journal Of Molecular Diagnostics; 14; 6; 11-2012; 613-6221525-1578CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://linkinghub.elsevier.com/retrieve/pii/S152515781200178Xinfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.jmoldx.2012.07.001info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:47:03Zoai:ri.conicet.gov.ar:11336/71523instacron: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:34982025-10-15 14:47:03.932CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv DNA methylation index and methylation profile of invasive ductal breast tumors
title DNA methylation index and methylation profile of invasive ductal breast tumors
spellingShingle DNA methylation index and methylation profile of invasive ductal breast tumors
Marzese, Diego Matías
Methylation Index
Retinoic Acid Receptor Beta
Tumor Protein P73
Breast Cancer
title_short DNA methylation index and methylation profile of invasive ductal breast tumors
title_full DNA methylation index and methylation profile of invasive ductal breast tumors
title_fullStr DNA methylation index and methylation profile of invasive ductal breast tumors
title_full_unstemmed DNA methylation index and methylation profile of invasive ductal breast tumors
title_sort DNA methylation index and methylation profile of invasive ductal breast tumors
dc.creator.none.fl_str_mv Marzese, Diego Matías
Hoon, Dave S.B.
Chong, Kelly K.
Gago, Francisco E.
Orozco, Javier Dario
Tello, Olga M.
Vargas Roig, Laura Maria
Roque Moreno, Maria
author Marzese, Diego Matías
author_facet Marzese, Diego Matías
Hoon, Dave S.B.
Chong, Kelly K.
Gago, Francisco E.
Orozco, Javier Dario
Tello, Olga M.
Vargas Roig, Laura Maria
Roque Moreno, Maria
author_role author
author2 Hoon, Dave S.B.
Chong, Kelly K.
Gago, Francisco E.
Orozco, Javier Dario
Tello, Olga M.
Vargas Roig, Laura Maria
Roque Moreno, Maria
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Methylation Index
Retinoic Acid Receptor Beta
Tumor Protein P73
Breast Cancer
topic Methylation Index
Retinoic Acid Receptor Beta
Tumor Protein P73
Breast Cancer
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Breast carcinogenesis is a multistep process that involves both genetic and epigenetic alterations. Identification of aberrantly methylated genes in breast tumors and their relation to clinical parameters can contribute to improved diagnostic, prognostic, and therapeutic decision making. Our objective in the present study was to identify the methylation status of 34 cancer-involved genes in invasive ductal carcinomas (IDC). Each of the 70 IDC cases analyzed had a unique methylation profile. The highest methylation frequency was detected in the WT1 (95.7%) and RASSF1 (71.4%) genes. Hierarchical cluster analysis revealed three clusters with different distribution of the prognostic factors tumor grade, lymph node metastasis, and proliferation rate. Methylation of TP73 was associated with high histological grade and high proliferation rate; methylation of RARB was associated with lymph node metastasis. Concurrent methylation of TP73 and RARB was associated with high histological grade, high proliferation rate, increased tumor size, and lymph node metastasis. Patients with more than six methylated genes had higher rates of relapse events and cancer deaths. In multivariate analysis, TP73 methylation and the methylation index were associated with disease outcome. Our results indicate that methylation index and methylation of TP73 and/or RARB are related to unfavorable prognostic factors in patients with IDC. These epigenetic markers should be validated in further studies to improve breast cancer management. © 2012 American Society for Investigative Pathology and the Association for Molecular Pathology.
Fil: Marzese, Diego Matías. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina. Universidad Nacional de Cuyo; Argentina
Fil: Hoon, Dave S.B.. Saint John's Health Center; Estados Unidos
Fil: Chong, Kelly K.. Saint John's Health Center; Estados Unidos
Fil: Gago, Francisco E.. Universidad Nacional de Cuyo; Argentina. Centro Médico de Mendoza; Argentina
Fil: Orozco, Javier Dario. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Cuyo; Argentina. Centro Médico de Mendoza; Argentina
Fil: Tello, Olga M.. Universidad Nacional de Cuyo; Argentina
Fil: Vargas Roig, Laura Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo; Argentina
Fil: Roque Moreno, Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina. Universidad Nacional de Cuyo; Argentina
description Breast carcinogenesis is a multistep process that involves both genetic and epigenetic alterations. Identification of aberrantly methylated genes in breast tumors and their relation to clinical parameters can contribute to improved diagnostic, prognostic, and therapeutic decision making. Our objective in the present study was to identify the methylation status of 34 cancer-involved genes in invasive ductal carcinomas (IDC). Each of the 70 IDC cases analyzed had a unique methylation profile. The highest methylation frequency was detected in the WT1 (95.7%) and RASSF1 (71.4%) genes. Hierarchical cluster analysis revealed three clusters with different distribution of the prognostic factors tumor grade, lymph node metastasis, and proliferation rate. Methylation of TP73 was associated with high histological grade and high proliferation rate; methylation of RARB was associated with lymph node metastasis. Concurrent methylation of TP73 and RARB was associated with high histological grade, high proliferation rate, increased tumor size, and lymph node metastasis. Patients with more than six methylated genes had higher rates of relapse events and cancer deaths. In multivariate analysis, TP73 methylation and the methylation index were associated with disease outcome. Our results indicate that methylation index and methylation of TP73 and/or RARB are related to unfavorable prognostic factors in patients with IDC. These epigenetic markers should be validated in further studies to improve breast cancer management. © 2012 American Society for Investigative Pathology and the Association for Molecular Pathology.
publishDate 2012
dc.date.none.fl_str_mv 2012-11
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/11336/71523
Marzese, Diego Matías; Hoon, Dave S.B.; Chong, Kelly K.; Gago, Francisco E.; Orozco, Javier Dario; et al.; DNA methylation index and methylation profile of invasive ductal breast tumors; American Society of Investigative Pathology; Journal Of Molecular Diagnostics; 14; 6; 11-2012; 613-622
1525-1578
CONICET Digital
CONICET
url http://hdl.handle.net/11336/71523
identifier_str_mv Marzese, Diego Matías; Hoon, Dave S.B.; Chong, Kelly K.; Gago, Francisco E.; Orozco, Javier Dario; et al.; DNA methylation index and methylation profile of invasive ductal breast tumors; American Society of Investigative Pathology; Journal Of Molecular Diagnostics; 14; 6; 11-2012; 613-622
1525-1578
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://linkinghub.elsevier.com/retrieve/pii/S152515781200178X
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.jmoldx.2012.07.001
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 American Society of Investigative Pathology
publisher.none.fl_str_mv American Society of Investigative Pathology
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
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instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
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repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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