Tarapara Bhoomi, Shah Franky
Molecular Diagnostic & Research Lab-3, Department of Cancer Biology, The Gujarat Cancer and Research Institute, Ahmedabad, Gujarat, 380016, India.
Clin Transl Oncol. 2025 Apr 30. doi: 10.1007/s12094-025-03934-w.
BRCA1/2 Mutations have been linked to an inherited risk of breast and ovarian cancer. However, gene silencing by promoter methylation of BRCA1 and BRCA2 has not been studied extensively.
Promoter methylation of BRCA1 and BRCA2 in the gDNA of 113 hereditary breast and ovarian cancer patients was carried out using methylation-specific qPCR.
The majority of patients showed higher methylation in BRCA2 than in BRCA1 and were significantly associated with hereditary breast and ovarian cancer Moreover, BRCA2 methylation was significantly associated with BRCA2 downregulation. Additionally, protein expression analysis in a subset of 25 patients with hypermethylated demonstrated a significant negative correlation between methylation status and protein expression for both BRCA1 and BRCA2.
BRCA1 and BRCA2 promoter methylation, particularly BRCA2, contributes to gene silencing and protein loss, and may act as key biomarkers for hereditary breast and ovarian cancer prognosis and therapy.
BRCA1/2突变与遗传性乳腺癌和卵巢癌风险相关。然而，BRCA1和BRCA2启动子甲基化导致的基因沉默尚未得到广泛研究。
采用甲基化特异性定量PCR检测113例遗传性乳腺癌和卵巢癌患者基因组DNA中BRCA1和BRCA2的启动子甲基化情况。
大多数患者BRCA2甲基化水平高于BRCA1，且与遗传性乳腺癌和卵巢癌显著相关。此外，BRCA2甲基化与BRCA2下调显著相关。另外，对25例高甲基化患者亚组的蛋白表达分析显示，BRCA1和BRCA2的甲基化状态与蛋白表达均呈显著负相关。
BRCA1和BRCA2启动子甲基化，尤其是BRCA2，导致基因沉默和蛋白缺失，可能是遗传性乳腺癌和卵巢癌预后及治疗的关键生物标志物。
