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Article

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

1
Department of Pathology, Portuguese Oncology Institute of Lisboa, 1099-023 Lisboa, Portugal
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Cancer Biology & Epigenetics Group—Research Center, Portuguese Oncology Institute of Porto (CI-IPOP), 4200-072 Porto, Portugal
3
Medical School, NOVA University, 1169-056 Lisbon, Portugal
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Department of Pathology, Portuguese Oncology Institute of Porto, 4200-072 Porto, Portugal
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Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar– University of Porto (ICBAS-UP), 4050-313 Porto, Portugal
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(8), 2715; https://doi.org/10.3390/ijms21082715
Received: 14 March 2020 / Revised: 29 March 2020 / Accepted: 11 April 2020 / Published: 14 April 2020
(This article belongs to the Special Issue DNA Repair in Human Disease)
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. View Full-Text
Keywords: male breast cancer; epigenetics; homologous recombination DNA repair; detection male breast cancer; epigenetics; homologous recombination DNA repair; detection
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MDPI and ACS Style

André, S.; P. Nunes, S.; Silva, F.; Henrique, R.; Félix, A.; Jerónimo, C. Analysis of Epigenetic Alterations in Homologous Recombination DNA Repair Genes in Male Breast Cancer. Int. J. Mol. Sci. 2020, 21, 2715. https://doi.org/10.3390/ijms21082715

AMA Style

André S, P. Nunes S, Silva F, Henrique R, Félix A, Jerónimo C. Analysis of Epigenetic Alterations in Homologous Recombination DNA Repair Genes in Male Breast Cancer. International Journal of Molecular Sciences. 2020; 21(8):2715. https://doi.org/10.3390/ijms21082715

Chicago/Turabian Style

André, Saudade, Sandra P. Nunes, Fernanda Silva, Rui Henrique, Ana Félix, and Carmen Jerónimo. 2020. "Analysis of Epigenetic Alterations in Homologous Recombination DNA Repair Genes in Male Breast Cancer" International Journal of Molecular Sciences 21, no. 8: 2715. https://doi.org/10.3390/ijms21082715

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