CDH1 methylation analysis in invasive lobular breast carcinomas with and without gene mutation

The proposed role of CDH1 (E-cadherin gene) methylation as a mechanism of gene inactivation in invasive lobular carcinoma (ILC) remains inconclusive. For many years, CDH1 promoter hypermethylation has been regarded as a mechanism for gene inactivation in ILC. However, this assumption has primarily r...

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Autores: González-Martínez, Silvia, Horvathova Kajabova, Viera, Pérez-Mies, Belén, Carretero, María Victoria, Caniego-Casas, Tamara, Sarrió, David, Moreno-Bueno, Gema, Gión, María, Perez-García, José, Cortés, Javier, Smolkova, Bozena, Palacios Calvo, José
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/382832
Acceso en línea:http://hdl.handle.net/10261/382832
Access Level:acceso abierto
Palabra clave:Breast cancer
Lobular carcinomas
CDH1
DNA methylation
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spelling CDH1 methylation analysis in invasive lobular breast carcinomas with and without gene mutationGonzález-Martínez, SilviaHorvathova Kajabova, VieraPérez-Mies, BelénCarretero, María VictoriaCaniego-Casas, TamaraSarrió, DavidMoreno-Bueno, GemaGión, MaríaPerez-García, JoséCortés, JavierSmolkova, BozenaPalacios Calvo, JoséBreast cancerLobular carcinomasCDH1DNA methylationThe proposed role of CDH1 (E-cadherin gene) methylation as a mechanism of gene inactivation in invasive lobular carcinoma (ILC) remains inconclusive. For many years, CDH1 promoter hypermethylation has been regarded as a mechanism for gene inactivation in ILC. However, this assumption has primarily relied on non-quantitative assays, which have reported CDH1 methylation frequencies ranging from 26 to 93% at CpG sites within the island region. Few studies employing quantitative methods and covering CpG island shores, regions of relatively low CpG density situated proximal to conventional promoter CpGs, have been conducted, revealing lower percentages of methylation ranging from 0 to 51%. Therefore, using the quantitative pyrosequencing method, we examined CDH1 methylation in the island region and shores in E-cadherin deficient ILC cases (15 with CDH1 mutation and 22 non-mutated), 19 cases of invasive breast carcinomas non-special type (IBC-NSTs), and five cases of usual ductal hyperplasia (UDH). Our analysis revealed CDH1 methylation frequencies ranging from 3 to 64%, with no significant increase in methylation levels in any group of ILCs (median = 12%) compared to IBC-NST (median = 15%). In addition, considering the poorly studied association between the number of tumor-infiltrating lymphocytes (TILs) and CDH1 methylation in breast cancer, we undertook a thorough analysis within our dataset. Our findings revealed a positive correlation between CDH1 methylation and the presence of TILs (r = 0.5; p-value < 0.05), shedding light on an aspect of breast cancer biology warranting further investigation. These findings challenge CDH1 methylation as a CDH1 inactivation mechanism in ILC and highlight TILs as a potential confounding factor in gene methylation.This study was funded by grants from the Instituto de Salud Carlos III (ISCIII) (PI19/01331 and PI22/01892) and was realized thanks to the Short-Term Scientific Mission Grant awarded by the Cost action CA19138 to SG-M.Peer reviewedSpringerInstituto de Salud Carlos IIIConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202520252024info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/382832reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)InglésThe underlying dataset has been published as supplementary material of the article in the publisher platform at DOI https://doi.org/10.1007/s00428-024-03814-8https://doi.org/10.1007/s00428-024-03814-8Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3828322026-05-22T06:33:51Z
dc.title.none.fl_str_mv CDH1 methylation analysis in invasive lobular breast carcinomas with and without gene mutation
title CDH1 methylation analysis in invasive lobular breast carcinomas with and without gene mutation
spellingShingle CDH1 methylation analysis in invasive lobular breast carcinomas with and without gene mutation
González-Martínez, Silvia
Breast cancer
Lobular carcinomas
CDH1
DNA methylation
title_short CDH1 methylation analysis in invasive lobular breast carcinomas with and without gene mutation
title_full CDH1 methylation analysis in invasive lobular breast carcinomas with and without gene mutation
title_fullStr CDH1 methylation analysis in invasive lobular breast carcinomas with and without gene mutation
title_full_unstemmed CDH1 methylation analysis in invasive lobular breast carcinomas with and without gene mutation
title_sort CDH1 methylation analysis in invasive lobular breast carcinomas with and without gene mutation
dc.creator.none.fl_str_mv González-Martínez, Silvia
Horvathova Kajabova, Viera
Pérez-Mies, Belén
Carretero, María Victoria
Caniego-Casas, Tamara
Sarrió, David
Moreno-Bueno, Gema
Gión, María
Perez-García, José
Cortés, Javier
Smolkova, Bozena
Palacios Calvo, José
author González-Martínez, Silvia
author_facet González-Martínez, Silvia
Horvathova Kajabova, Viera
Pérez-Mies, Belén
Carretero, María Victoria
Caniego-Casas, Tamara
Sarrió, David
Moreno-Bueno, Gema
Gión, María
Perez-García, José
Cortés, Javier
Smolkova, Bozena
Palacios Calvo, José
author_role author
author2 Horvathova Kajabova, Viera
Pérez-Mies, Belén
Carretero, María Victoria
Caniego-Casas, Tamara
Sarrió, David
Moreno-Bueno, Gema
Gión, María
Perez-García, José
Cortés, Javier
Smolkova, Bozena
Palacios Calvo, José
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Instituto de Salud Carlos III
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Breast cancer
Lobular carcinomas
CDH1
DNA methylation
topic Breast cancer
Lobular carcinomas
CDH1
DNA methylation
description The proposed role of CDH1 (E-cadherin gene) methylation as a mechanism of gene inactivation in invasive lobular carcinoma (ILC) remains inconclusive. For many years, CDH1 promoter hypermethylation has been regarded as a mechanism for gene inactivation in ILC. However, this assumption has primarily relied on non-quantitative assays, which have reported CDH1 methylation frequencies ranging from 26 to 93% at CpG sites within the island region. Few studies employing quantitative methods and covering CpG island shores, regions of relatively low CpG density situated proximal to conventional promoter CpGs, have been conducted, revealing lower percentages of methylation ranging from 0 to 51%. Therefore, using the quantitative pyrosequencing method, we examined CDH1 methylation in the island region and shores in E-cadherin deficient ILC cases (15 with CDH1 mutation and 22 non-mutated), 19 cases of invasive breast carcinomas non-special type (IBC-NSTs), and five cases of usual ductal hyperplasia (UDH). Our analysis revealed CDH1 methylation frequencies ranging from 3 to 64%, with no significant increase in methylation levels in any group of ILCs (median = 12%) compared to IBC-NST (median = 15%). In addition, considering the poorly studied association between the number of tumor-infiltrating lymphocytes (TILs) and CDH1 methylation in breast cancer, we undertook a thorough analysis within our dataset. Our findings revealed a positive correlation between CDH1 methylation and the presence of TILs (r = 0.5; p-value < 0.05), shedding light on an aspect of breast cancer biology warranting further investigation. These findings challenge CDH1 methylation as a CDH1 inactivation mechanism in ILC and highlight TILs as a potential confounding factor in gene methylation.
publishDate 2024
dc.date.none.fl_str_mv 2024
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/382832
url http://hdl.handle.net/10261/382832
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI https://doi.org/10.1007/s00428-024-03814-8
https://doi.org/10.1007/s00428-024-03814-8
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Springer
publisher.none.fl_str_mv Springer
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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