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Analysis of Epigenetic Alterations in Homologous Recombination DNA Repair Genes in Male Breast Cancer

Background: Male breast cancer (BC) is a distinct neoplasm with low but rising incidence, frequently diagnosed as advanced stage disease. Considering the relevance of altered homologous recombination repair (HRR) in male BC, we aimed to explore the biomarker potential of aberrant promoter methylatio...

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Autores principales: André, Saudade, P. Nunes, Sandra, Silva, Fernanda, Henrique, Rui, Félix, Ana, Jerónimo, Carmen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7215617/
https://www.ncbi.nlm.nih.gov/pubmed/32295201
http://dx.doi.org/10.3390/ijms21082715
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author André, Saudade
P. Nunes, Sandra
Silva, Fernanda
Henrique, Rui
Félix, Ana
Jerónimo, Carmen
author_facet André, Saudade
P. Nunes, Sandra
Silva, Fernanda
Henrique, Rui
Félix, Ana
Jerónimo, Carmen
author_sort André, Saudade
collection PubMed
description Background: Male breast cancer (BC) is a distinct neoplasm with low but rising incidence, frequently diagnosed as advanced stage disease. Considering the relevance of altered homologous recombination repair (HRR) in male BC, we aimed to explore the biomarker potential of aberrant promoter methylation of ATM, BRCA1, PALB2, RAD51B, and XRCC3. Methods: Formalin-fixed paraffin-embedded (FFPE) tissue samples from 128 male BC patients, paired adjacent normal tissue and 19 gynecomastia cases were collected and assessed by quantitative methylation-specific PCR (qMSP). Non-parametric tests were used to compare methylation levels between tumor and non-tumor samples and to seek for associations with clinicopathological variables. Results: Only RAD51B and XRCC3 disclosed significant differences between tumor and gynecomastia (p < 0.0001 and p = 0.020, respectively). Assembled in a panel, RAD51B and XRCC3 promoter methylation discriminated male BC from gynecomastia with 91.5% sensitivity, 89.5% specificity, and 91.2% accuracy. Moreover, promoter methylation levels were lower in paired non-tumor tissues, comparing to tumor samples. No associations were found between epigenetic alterations and clinicopathological features, as well as with RAD51 and XRCC3 immunoexpression and methylation levels. Conclusion: Quantitative promoter methylation of RAD51B and XRCC3 constitutes a promising and accurate biomarker for male BC. Validation in larger series and in liquid biopsies is warranted to confirm its usefulness in detection and monitoring settings.
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spelling pubmed-72156172020-05-22 Analysis of Epigenetic Alterations in Homologous Recombination DNA Repair Genes in Male Breast Cancer André, Saudade P. Nunes, Sandra Silva, Fernanda Henrique, Rui Félix, Ana Jerónimo, Carmen Int J Mol Sci Article Background: Male breast cancer (BC) is a distinct neoplasm with low but rising incidence, frequently diagnosed as advanced stage disease. Considering the relevance of altered homologous recombination repair (HRR) in male BC, we aimed to explore the biomarker potential of aberrant promoter methylation of ATM, BRCA1, PALB2, RAD51B, and XRCC3. Methods: Formalin-fixed paraffin-embedded (FFPE) tissue samples from 128 male BC patients, paired adjacent normal tissue and 19 gynecomastia cases were collected and assessed by quantitative methylation-specific PCR (qMSP). Non-parametric tests were used to compare methylation levels between tumor and non-tumor samples and to seek for associations with clinicopathological variables. Results: Only RAD51B and XRCC3 disclosed significant differences between tumor and gynecomastia (p < 0.0001 and p = 0.020, respectively). Assembled in a panel, RAD51B and XRCC3 promoter methylation discriminated male BC from gynecomastia with 91.5% sensitivity, 89.5% specificity, and 91.2% accuracy. Moreover, promoter methylation levels were lower in paired non-tumor tissues, comparing to tumor samples. No associations were found between epigenetic alterations and clinicopathological features, as well as with RAD51 and XRCC3 immunoexpression and methylation levels. Conclusion: Quantitative promoter methylation of RAD51B and XRCC3 constitutes a promising and accurate biomarker for male BC. Validation in larger series and in liquid biopsies is warranted to confirm its usefulness in detection and monitoring settings. MDPI 2020-04-14 /pmc/articles/PMC7215617/ /pubmed/32295201 http://dx.doi.org/10.3390/ijms21082715 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
André, Saudade
P. Nunes, Sandra
Silva, Fernanda
Henrique, Rui
Félix, Ana
Jerónimo, Carmen
Analysis of Epigenetic Alterations in Homologous Recombination DNA Repair Genes in Male Breast Cancer
title Analysis of Epigenetic Alterations in Homologous Recombination DNA Repair Genes in Male Breast Cancer
title_full Analysis of Epigenetic Alterations in Homologous Recombination DNA Repair Genes in Male Breast Cancer
title_fullStr Analysis of Epigenetic Alterations in Homologous Recombination DNA Repair Genes in Male Breast Cancer
title_full_unstemmed Analysis of Epigenetic Alterations in Homologous Recombination DNA Repair Genes in Male Breast Cancer
title_short Analysis of Epigenetic Alterations in Homologous Recombination DNA Repair Genes in Male Breast Cancer
title_sort analysis of epigenetic alterations in homologous recombination dna repair genes in male breast cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7215617/
https://www.ncbi.nlm.nih.gov/pubmed/32295201
http://dx.doi.org/10.3390/ijms21082715
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