BRCA1 Promoter Hypermethylation in Malignant Breast Tumors and in the Histologically Normal Adjacent Tissues to the Tumors: Exploring Its Potential as a Biomarker and Its Clinical Significance in a Translational Approach
The hypermethylation status of the promoter region of the breast cancer 1 (<i>BRCA1)</i>, a well-known tumor suppressor gene, has been extensively investigated in the last two decades as a potential biomarker for breast cancer. In this retrospective study, we investigated the prevalence...
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MDPI AG
2023-08-01
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| Online Access: | https://www.mdpi.com/2073-4425/14/9/1680 |
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| author | Yassire Oubaddou Mohamed Oukabli Salma Fenniche Abderrahim Elktaibi Mohamed Reda Elochi Abderrahmane Al Bouzidi Zineb Qmichou Nadia Dakka Caroline Diorio Antje Richter Youssef Bakri Rabii Ameziane El Hassani |
| author_facet | Yassire Oubaddou Mohamed Oukabli Salma Fenniche Abderrahim Elktaibi Mohamed Reda Elochi Abderrahmane Al Bouzidi Zineb Qmichou Nadia Dakka Caroline Diorio Antje Richter Youssef Bakri Rabii Ameziane El Hassani |
| author_sort | Yassire Oubaddou |
| collection | DOAJ |
| description | The hypermethylation status of the promoter region of the breast cancer 1 (<i>BRCA1)</i>, a well-known tumor suppressor gene, has been extensively investigated in the last two decades as a potential biomarker for breast cancer. In this retrospective study, we investigated the prevalence of <i>BRCA1</i> promoter methylation in 84 human breast tissues, and we correlated this epigenetic silencing with the clinical and histopathological parameters of breast cancer. We used methylation-specific PCR (MSP) to analyze BRCA1 promoter hypermethylation in 48 malignant breast tumors (MBTs), 15 normal adjacent tissues (NATs), and 21 benign breast lesions (BBLs). The results showed that <i>BRCA1</i> promoter hypermethylation was higher in MBTs (20/48; 41.67%) and NATs (7/15; 46.67%) compared to BBLs (4/21; 19.05%). The high percentage of BRCA1 hypermethylation in the histologically normal adjacent tissues to the tumors (NATs) suggests the involvement of this epigenetic silencing as a potential biomarker of the early genomic instability in NATs surrounding the tumors. The detection of BRCA1 promoter hypermethylation in BBLs reinforces this suggestion, knowing that a non-negligible rate of benign breast lesions was reported to evolve into cancer. Moreover, our results indicated that the <i>BRCA1</i> promoter hypermethylated group of MBTs exhibited higher rates of aggressive features, as indicated by the SBR III grade (14/19; 73.68%), elevated Ki67 levels (13/16; 81.25%), and Her2 receptor overexpression (5/20; 25%). Finally, we observed a concordance (60%) in <i>BRCA1</i> promoter hypermethylation status between malignant breast tumors and their paired histologically normal adjacent tissues. This study highlights the role of BRCA1 promoter hypermethylation as a potential useful biomarker of aggressiveness in MBTs and as an early marker of genomic instability in both histological NATs and BBLs. |
| first_indexed | 2024-03-10T22:43:00Z |
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| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-10T22:43:00Z |
| publishDate | 2023-08-01 |
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| series | Genes |
| spelling | doaj.art-0ffe3a6732a94f3788ce51473cf1c1112023-11-19T10:52:11ZengMDPI AGGenes2073-44252023-08-01149168010.3390/genes14091680BRCA1 Promoter Hypermethylation in Malignant Breast Tumors and in the Histologically Normal Adjacent Tissues to the Tumors: Exploring Its Potential as a Biomarker and Its Clinical Significance in a Translational ApproachYassire Oubaddou0Mohamed Oukabli1Salma Fenniche2Abderrahim Elktaibi3Mohamed Reda Elochi4Abderrahmane Al Bouzidi5Zineb Qmichou6Nadia Dakka7Caroline Diorio8Antje Richter9Youssef Bakri10Rabii Ameziane El Hassani11Laboratory of Biology of Human Pathologies (BioPatH), Faculty of Sciences, Mohammed V University in Rabat, Rabat 10001, MoroccoService of Anatomical Pathology, Military Hospital of Instruction Mohammed V (HMIMV-R), Faculty of Medicine and Pharmacy, Mohammed V University in Rabat, Rabat 10001, MoroccoLaboratory of Biology of Human Pathologies (BioPatH), Faculty of Sciences, Mohammed V University in Rabat, Rabat 10001, MoroccoService of Anatomical Pathology, Military Hospital of Instruction Mohammed V (HMIMV-R), Faculty of Medicine and Pharmacy, Mohammed V University in Rabat, Rabat 10001, MoroccoService of Anatomical Pathology, Military Hospital of Instruction Mohammed V (HMIMV-R), Faculty of Medicine and Pharmacy, Mohammed V University in Rabat, Rabat 10001, MoroccoCabinet Anatomie Pathologique Essaada, Rabat 10001, MoroccoMedical Biotechnology Center, Moroccan Foundation for Advanced Science, Innovation and Research (MAScIR), Rabat 10001, MoroccoLaboratory of Biology of Human Pathologies (BioPatH), Faculty of Sciences, Mohammed V University in Rabat, Rabat 10001, MoroccoCancer Research Center, CHU de Québec—Université Laval Research Center, Oncology Division, Québec, QC G1R 3S3, CanadaInstitute for Genetics, University Giessen, 35392 Giessen, GermanyLaboratory of Biology of Human Pathologies (BioPatH), Faculty of Sciences, Mohammed V University in Rabat, Rabat 10001, MoroccoLaboratory of Biology of Human Pathologies (BioPatH), Faculty of Sciences, Mohammed V University in Rabat, Rabat 10001, MoroccoThe hypermethylation status of the promoter region of the breast cancer 1 (<i>BRCA1)</i>, a well-known tumor suppressor gene, has been extensively investigated in the last two decades as a potential biomarker for breast cancer. In this retrospective study, we investigated the prevalence of <i>BRCA1</i> promoter methylation in 84 human breast tissues, and we correlated this epigenetic silencing with the clinical and histopathological parameters of breast cancer. We used methylation-specific PCR (MSP) to analyze BRCA1 promoter hypermethylation in 48 malignant breast tumors (MBTs), 15 normal adjacent tissues (NATs), and 21 benign breast lesions (BBLs). The results showed that <i>BRCA1</i> promoter hypermethylation was higher in MBTs (20/48; 41.67%) and NATs (7/15; 46.67%) compared to BBLs (4/21; 19.05%). The high percentage of BRCA1 hypermethylation in the histologically normal adjacent tissues to the tumors (NATs) suggests the involvement of this epigenetic silencing as a potential biomarker of the early genomic instability in NATs surrounding the tumors. The detection of BRCA1 promoter hypermethylation in BBLs reinforces this suggestion, knowing that a non-negligible rate of benign breast lesions was reported to evolve into cancer. Moreover, our results indicated that the <i>BRCA1</i> promoter hypermethylated group of MBTs exhibited higher rates of aggressive features, as indicated by the SBR III grade (14/19; 73.68%), elevated Ki67 levels (13/16; 81.25%), and Her2 receptor overexpression (5/20; 25%). Finally, we observed a concordance (60%) in <i>BRCA1</i> promoter hypermethylation status between malignant breast tumors and their paired histologically normal adjacent tissues. This study highlights the role of BRCA1 promoter hypermethylation as a potential useful biomarker of aggressiveness in MBTs and as an early marker of genomic instability in both histological NATs and BBLs.https://www.mdpi.com/2073-4425/14/9/1680BRCA1 promoter hypermethylationbreast cancersnormal adjacent tissuebenign breast lesionsmethylation-specific PCRbiomarker |
| spellingShingle | Yassire Oubaddou Mohamed Oukabli Salma Fenniche Abderrahim Elktaibi Mohamed Reda Elochi Abderrahmane Al Bouzidi Zineb Qmichou Nadia Dakka Caroline Diorio Antje Richter Youssef Bakri Rabii Ameziane El Hassani BRCA1 Promoter Hypermethylation in Malignant Breast Tumors and in the Histologically Normal Adjacent Tissues to the Tumors: Exploring Its Potential as a Biomarker and Its Clinical Significance in a Translational Approach Genes BRCA1 promoter hypermethylation breast cancers normal adjacent tissue benign breast lesions methylation-specific PCR biomarker |
| title | BRCA1 Promoter Hypermethylation in Malignant Breast Tumors and in the Histologically Normal Adjacent Tissues to the Tumors: Exploring Its Potential as a Biomarker and Its Clinical Significance in a Translational Approach |
| title_full | BRCA1 Promoter Hypermethylation in Malignant Breast Tumors and in the Histologically Normal Adjacent Tissues to the Tumors: Exploring Its Potential as a Biomarker and Its Clinical Significance in a Translational Approach |
| title_fullStr | BRCA1 Promoter Hypermethylation in Malignant Breast Tumors and in the Histologically Normal Adjacent Tissues to the Tumors: Exploring Its Potential as a Biomarker and Its Clinical Significance in a Translational Approach |
| title_full_unstemmed | BRCA1 Promoter Hypermethylation in Malignant Breast Tumors and in the Histologically Normal Adjacent Tissues to the Tumors: Exploring Its Potential as a Biomarker and Its Clinical Significance in a Translational Approach |
| title_short | BRCA1 Promoter Hypermethylation in Malignant Breast Tumors and in the Histologically Normal Adjacent Tissues to the Tumors: Exploring Its Potential as a Biomarker and Its Clinical Significance in a Translational Approach |
| title_sort | brca1 promoter hypermethylation in malignant breast tumors and in the histologically normal adjacent tissues to the tumors exploring its potential as a biomarker and its clinical significance in a translational approach |
| topic | BRCA1 promoter hypermethylation breast cancers normal adjacent tissue benign breast lesions methylation-specific PCR biomarker |
| url | https://www.mdpi.com/2073-4425/14/9/1680 |
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