Roadmap of DNA methylation in breast cancer identifies novel prognostic biomarkers

Detalhes bibliográficos
Autor(a) principal: Almeida, Bernardo P. De
Data de Publicação: 2019
Outros Autores: Apolónio, Joana Dias, Binnie, Alexandra, Castelo Branco, Pedro
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/48408
Resumo: © The Author(s). 2019. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
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spelling Roadmap of DNA methylation in breast cancer identifies novel prognostic biomarkersBiomarkersBreast cancerDNA methylationDiagnosticPrognostic© The Author(s). 2019. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background: Breast cancer is a highly heterogeneous disease resulting in diverse clinical behaviours and therapeutic responses. DNA methylation is a major epigenetic alteration that is commonly perturbed in cancers. The aim of this study is to characterize the relationship between DNA methylation and aberrant gene expression in breast cancer. Methods: We analysed DNA methylation and gene expression profiles from breast cancer tissue and matched normal tissue in The Cancer Genome Atlas (TCGA). Genome-wide differential methylation analysis and methylation-gene expression correlation was performed. Gene expression changes were subsequently validated in the METABRIC dataset. The Oncoscore tool was used to identify genes that had previously been associated with cancer in the literature. A subset of genes that had not previously been studied in cancer was chosen for further analysis. Results: We identified 368 CpGs that were differentially methylated between tumor and normal breast tissue (∆β > 0.4). Hypermethylated CpGs were overrepresented in tumor tissue and were found predominantly (56%) in upstream promoter regions. Conversely, hypomethylated CpG sites were found primarily in the gene body (66%). Expression analysis revealed that 209 of the differentially-methylated CpGs were located in 169 genes that were differently expressed between normal and breast tumor tissue. Methylation-expression correlations were predominantly negative (70%) for promoter CpG sites and positive (74%) for gene body CpG sites. Among these differentially-methylated and differentially-expressed genes, we identified 7 that had not previously been studied in any form of cancer. Three of these, TDRD10, PRAC2 and TMEM132C, contained CpG sites that showed diagnostic and prognostic value in breast cancer, particularly in estrogen-receptor (ER)-positive samples. A pan-cancer analysis confirmed differential expression of these genes together with diagnostic and prognostic value of their respective CpG sites in multiple cancer types. Conclusion: We have identified 368 DNA methylation changes that characterize breast cancer tumor tissue, of which 209 are associated with genes that are differentially-expressed in the same samples. Novel DNA methylation markers were identified, of which cg12374721 (PRAC2), cg18081940 (TDRD10) and cg04475027 (TMEM132C) show promise as diagnostic and prognostic markers in breast cancer as well as other cancer types.This work was supported by the research grant UID/BIM/04773/2013 CBMR from FCT and Maratona da Saúde. JA is supported by PD/BD/105899/2014 FCT fellowship.Springer NatureRepositório da Universidade de LisboaAlmeida, Bernardo P. DeApolónio, Joana DiasBinnie, AlexandraCastelo Branco, Pedro2021-06-08T12:54:58Z20192019-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/48408engBMC Cancer. 2019 Mar 12;19(1):21910.1186/s12885-019-5403-01471-2407info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T16:51:47Zoai:repositorio.ul.pt:10451/48408Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:00:18.479846Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Roadmap of DNA methylation in breast cancer identifies novel prognostic biomarkers
title Roadmap of DNA methylation in breast cancer identifies novel prognostic biomarkers
spellingShingle Roadmap of DNA methylation in breast cancer identifies novel prognostic biomarkers
Almeida, Bernardo P. De
Biomarkers
Breast cancer
DNA methylation
Diagnostic
Prognostic
title_short Roadmap of DNA methylation in breast cancer identifies novel prognostic biomarkers
title_full Roadmap of DNA methylation in breast cancer identifies novel prognostic biomarkers
title_fullStr Roadmap of DNA methylation in breast cancer identifies novel prognostic biomarkers
title_full_unstemmed Roadmap of DNA methylation in breast cancer identifies novel prognostic biomarkers
title_sort Roadmap of DNA methylation in breast cancer identifies novel prognostic biomarkers
author Almeida, Bernardo P. De
author_facet Almeida, Bernardo P. De
Apolónio, Joana Dias
Binnie, Alexandra
Castelo Branco, Pedro
author_role author
author2 Apolónio, Joana Dias
Binnie, Alexandra
Castelo Branco, Pedro
author2_role author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Almeida, Bernardo P. De
Apolónio, Joana Dias
Binnie, Alexandra
Castelo Branco, Pedro
dc.subject.por.fl_str_mv Biomarkers
Breast cancer
DNA methylation
Diagnostic
Prognostic
topic Biomarkers
Breast cancer
DNA methylation
Diagnostic
Prognostic
description © The Author(s). 2019. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
publishDate 2019
dc.date.none.fl_str_mv 2019
2019-01-01T00:00:00Z
2021-06-08T12:54:58Z
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 http://hdl.handle.net/10451/48408
url http://hdl.handle.net/10451/48408
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv BMC Cancer. 2019 Mar 12;19(1):219
10.1186/s12885-019-5403-0
1471-2407
dc.rights.driver.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 Nature
publisher.none.fl_str_mv Springer Nature
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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