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

被引:6
|
作者
Andre, Saudade [1 ]
Nunes, Sandra P. [2 ]
Silva, Fernanda [3 ]
Henrique, Rui [2 ,4 ,5 ]
Felix, Ana [1 ,3 ]
Jeronimo, Carmen [2 ,5 ]
机构
[1] Portuguese Oncol Inst Lisboa, Dept Pathol, P-1099023 Lisbon, Portugal
[2] Portuguese Oncol Inst Porto CI IPOP, Canc Biol & Epigenet Grp, Res Ctr, P-4200072 Porto, Portugal
[3] NOVA Univ, Med Sch, P-1169056 Lisbon, Portugal
[4] Portuguese Oncol Inst Porto, Dept Pathol, P-4200072 Porto, Portugal
[5] Univ Porto ICBAS UP, Inst Biomed Sci Abel Salazar, Dept Pathol & Mol Immunol, P-4050313 Porto, Portugal
关键词
male breast cancer; epigenetics; homologous recombination DNA repair; detection; METHYLATION; INSIGHTS;
D O I
10.3390/ijms21082715
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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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页数:12
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