Oubaddou Yassire, Oukabli Mohamed, Fenniche Salma, Elktaibi Abderrahim, Elochi Mohamed Reda, Al Bouzidi Abderrahmane, Qmichou Zineb, Dakka Nadia, Diorio Caroline, Richter Antje, Bakri Youssef, Ameziane El Hassani Rabii
Laboratory of Biology of Human Pathologies (BioPatH), Faculty of Sciences, Mohammed V University in Rabat, Rabat 10001, Morocco.
Service of Anatomical Pathology, Military Hospital of Instruction Mohammed V (HMIMV-R), Faculty of Medicine and Pharmacy, Mohammed V University in Rabat, Rabat 10001, Morocco.
Genes (Basel). 2023 Aug 25;14(9):1680. doi: 10.3390/genes14091680.
The hypermethylation status of the promoter region of the breast cancer 1 (, 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 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 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 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 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.
乳腺癌1（BRCA1）是一种著名的肿瘤抑制基因，在过去二十年中，其启动子区域的高甲基化状态作为乳腺癌的潜在生物标志物受到了广泛研究。在这项回顾性研究中，我们调查了84个人类乳腺组织中BRCA1启动子甲基化的发生率，并将这种表观遗传沉默与乳腺癌的临床和组织病理学参数相关联。我们使用甲基化特异性PCR（MSP）分析了48例恶性乳腺肿瘤（MBT）、15例正常相邻组织（NAT）和21例良性乳腺病变（BBL）中BRCA1启动子的高甲基化情况。结果显示，与BBL（4/21；19.05%）相比，MBT（20/48；41.67%）和NAT（7/15；46.67%）中BRCA1启动子高甲基化水平更高。肿瘤组织学上正常的相邻组织（NAT）中BRCA1高甲基化比例较高，这表明这种表观遗传沉默可能参与了肿瘤周围NAT早期基因组不稳定的潜在生物标志物的形成。在BBL中检测到BRCA1启动子高甲基化进一步支持了这一观点，因为据报道有不可忽视比例的良性乳腺病变会发展为癌症。此外，我们的结果表明，MBT中BRCA1启动子高甲基化组表现出更高的侵袭性特征，如SBR III级（14/19；73.68%）、Ki67水平升高（13/16；81.25%）和Her2受体过表达（5/20；25%）。最后，我们观察到恶性乳腺肿瘤与其配对的组织学正常相邻组织之间BRCA1启动子高甲基化状态的一致性为60%。本研究强调了BRCA1启动子高甲基化作为MBT侵袭性的潜在有用生物标志物以及组织学NAT和BBL基因组不稳定早期标志物的作用。
