Epigenomic alterations in breast carcinoma from primary tumor to locoregional recurrences.

<h4>Introduction</h4>Epigenetic modifications such as aberrant DNA methylation has long been associated with tumorogenesis. Little is known, however, about how these modifications appear in cancer progression. Comparing the methylome of breast carcinomas and locoregional evolutions could...

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Autores principales:	Matahi Moarii, Alice Pinheiro, Brigitte Sigal-Zafrani, Alain Fourquet, Martial Caly, Nicolas Servant, Véronique Stoven, Jean-Philippe Vert, Fabien Reyal
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ee9e88f1ffb147128515b66372642286
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spelling	oai:doaj.org-article:ee9e88f1ffb147128515b663726422862021-11-25T06:05:51ZEpigenomic alterations in breast carcinoma from primary tumor to locoregional recurrences.1932-620310.1371/journal.pone.0103986https://doaj.org/article/ee9e88f1ffb147128515b663726422862014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25098247/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Introduction</h4>Epigenetic modifications such as aberrant DNA methylation has long been associated with tumorogenesis. Little is known, however, about how these modifications appear in cancer progression. Comparing the methylome of breast carcinomas and locoregional evolutions could shed light on this process.<h4>Methods</h4>The methylome profiles of 48 primary breast carcinomas (PT) and their matched axillary metastases (PT/AM pairs, 20 cases), local recurrences (PT/LR pairs, 17 cases) or contralateral breast carcinomas (PT/CL pairs, 11 cases) were analyzed. Univariate and multivariate analyzes were performed to determine differentially methylated probes (DMPs), and a similarity score was defined to compare methylation profiles. Correlation with copy-number based score was calculated and metastatic-free survival was compared between methods.<h4>Results</h4>49 DMPs were found for the PT/AM set, but none for the others (FDR < 5%). Hierarchical clustering clustered 75% of the PT/AM, 47% of the PT/LR, and none of the PT/CL pairs together. A methylation-based score (MS) was defined as a clonality measure. The PT/AM set contained a high proportion of clonal pairs while PT/LR pairs were evenly split between high and low MS score, suggesting two groups: true recurrences (TR) and new primary tumors (NP). CL were classified as new tumors. MS score was significantly correlated with copy-number based scores. There was no significant difference between the metastatic-free survival of groups of patients based on different classifications.<h4>Conclusion</h4>Epigenomic alterations are well suited to study clonality and track cancer progression. Methylation-based classification of TR and NP performed as well as clinical and copy-number based methods suggesting that these phenomenons are tightly linked.Matahi MoariiAlice PinheiroBrigitte Sigal-ZafraniAlain FourquetMartial CalyNicolas ServantVéronique StovenJean-Philippe VertFabien ReyalPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 8, p e103986 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Matahi Moarii Alice Pinheiro Brigitte Sigal-Zafrani Alain Fourquet Martial Caly Nicolas Servant Véronique Stoven Jean-Philippe Vert Fabien Reyal Epigenomic alterations in breast carcinoma from primary tumor to locoregional recurrences.
description	<h4>Introduction</h4>Epigenetic modifications such as aberrant DNA methylation has long been associated with tumorogenesis. Little is known, however, about how these modifications appear in cancer progression. Comparing the methylome of breast carcinomas and locoregional evolutions could shed light on this process.<h4>Methods</h4>The methylome profiles of 48 primary breast carcinomas (PT) and their matched axillary metastases (PT/AM pairs, 20 cases), local recurrences (PT/LR pairs, 17 cases) or contralateral breast carcinomas (PT/CL pairs, 11 cases) were analyzed. Univariate and multivariate analyzes were performed to determine differentially methylated probes (DMPs), and a similarity score was defined to compare methylation profiles. Correlation with copy-number based score was calculated and metastatic-free survival was compared between methods.<h4>Results</h4>49 DMPs were found for the PT/AM set, but none for the others (FDR < 5%). Hierarchical clustering clustered 75% of the PT/AM, 47% of the PT/LR, and none of the PT/CL pairs together. A methylation-based score (MS) was defined as a clonality measure. The PT/AM set contained a high proportion of clonal pairs while PT/LR pairs were evenly split between high and low MS score, suggesting two groups: true recurrences (TR) and new primary tumors (NP). CL were classified as new tumors. MS score was significantly correlated with copy-number based scores. There was no significant difference between the metastatic-free survival of groups of patients based on different classifications.<h4>Conclusion</h4>Epigenomic alterations are well suited to study clonality and track cancer progression. Methylation-based classification of TR and NP performed as well as clinical and copy-number based methods suggesting that these phenomenons are tightly linked.
format	article
author	Matahi Moarii Alice Pinheiro Brigitte Sigal-Zafrani Alain Fourquet Martial Caly Nicolas Servant Véronique Stoven Jean-Philippe Vert Fabien Reyal
author_facet	Matahi Moarii Alice Pinheiro Brigitte Sigal-Zafrani Alain Fourquet Martial Caly Nicolas Servant Véronique Stoven Jean-Philippe Vert Fabien Reyal
author_sort	Matahi Moarii
title	Epigenomic alterations in breast carcinoma from primary tumor to locoregional recurrences.
title_short	Epigenomic alterations in breast carcinoma from primary tumor to locoregional recurrences.
title_full	Epigenomic alterations in breast carcinoma from primary tumor to locoregional recurrences.
title_fullStr	Epigenomic alterations in breast carcinoma from primary tumor to locoregional recurrences.
title_full_unstemmed	Epigenomic alterations in breast carcinoma from primary tumor to locoregional recurrences.
title_sort	epigenomic alterations in breast carcinoma from primary tumor to locoregional recurrences.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/ee9e88f1ffb147128515b66372642286
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Epigenomic alterations in breast carcinoma from primary tumor to locoregional recurrences.

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