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. 2025 Oct;27(10):3911-3923.
doi: 10.1007/s12094-025-03934-w. Epub 2025 Apr 30.

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

Bhoomi Tarapara  1 , Franky Shah  2
Affiliations

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

Bhoomi Tarapara et al. Clin Transl Oncol. 2025 Oct.

Abstract

Background: 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.

Materials and methods: Promoter methylation of BRCA1 and BRCA2 in the gDNA of 113 hereditary breast and ovarian cancer patients was carried out using methylation-specific qPCR.

Results: 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.

Conclusion: 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.

Keywords: DNA methylation; Epigenetic events; Hereditary breast and ovarian cancer; Peripheral blood; Real time PCR.

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Conflict of interest statement

Declarations. Conflicts of interest: The authors declare no competing interests. Ethical approval: The present study was approved by The Institutional Review Board Committee (IRB) of The Gujarat Cancer & Research Institute (EC/BHR/10/2022). Informed consent statement: Informed consent was obtained from all subjects involved in the study.

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