Franky Shah

BRCA1/2 methylation and expression dynamics in hereditary breast and ovarian cancer: insights from gene, protein, and TCGA analysis

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.

Role of MRE11 in DNA damage repair pathway dynamics and its diagnostic and prognostic significance in hereditary breast and ovarian cancer

DNA damage repair pathway genes are key components for maintaining genomic stability and are mainly associated with hereditary breast and ovarian cancer. The present study aimed to investigate the gene expression profile of DNA damage repair pathway genes, including BRCA1, BRCA2, ATM, TP53, CHEK2, MRE11, RAD50, BARD1, PALB2, and NBN, in hereditary breast and ovarian cancer patients using quantitative real-time PCR. The study showed significant upregulation of most DNA damage repair genes in HBOC patients compared to controls, except MRE11, which was downregulated. Receiver operating characteristic (ROC) curve analysis revealed that MRE11 (p < 0.001), BRCA1 (p < 0.001), BRCA2 (p < 0.001), and PALB2 (p < 0.001) can be used as potential diagnostic biomarkers for hereditary breast and ovarian cancer. Spearman correlation analysis showed that RAD50 was significantly associated with the BRCA1/2 mutation status (p = 0.05). Furthermore, bivariate analysis revealed a strong positive correlation between BARD1 gene expression and the expression of BRCA1, PALB2, and NBN genes. Kaplan-Meier survival analysis showed that reduces expression of the MRE11 gene was associated with better overall survival. The study findings may lead to a better understanding of the molecular mechanisms underlying hereditary breast and ovarian cancer, suggesting its role as a potential diagnostic and prognostic marker.