Constitutional BRCA1 promoter methylation as a biomarker for ovarian cancer risk.

Constitutional *BRCA1* promoter methylation as an ovarian cancer risk factor (epimutation)

This JCO Precision Oncology study evaluates the clinical relevance of constitutional BRCA1 promoter methylation in 473 ovarian cancer patients (AGO-TR1 study). Constitutional epimutations, present across normal tissues including blood from early development, emerge as a biomarker for BRCA1-associated cancer risk, with assessed frequency, clinical characteristics, and diagnostic implications distinct from sequence variants.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

Constitutional BRCA1 epimutations represent a significant diagnostic blind spot: undetected by standard sequencing panels and absent from variant databases. This study reinforces the case for including methylation analysis in ovarian cancer patients with negative sequencing results.

Clinical impact: 3/3 · Evidence strength: 2/3 · Novelty: 2/2 · Sample size: 1/1 · Publication status: 1/1 → Total: 9/10