SynthesisJournal of the National Cancer Institute2020
BRCA1 Promoter Methylation and Clinical Outcomes in Ovarian Cancer: An Individual Patient Data Meta-Analysis.
Synthesis in Journal of the National Cancer Institute, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 61 citations in OpenAlex.
- Olaparib in HR-deficient, metastatic triple-negative breast and platinum-sensitive relapsed ovarian cancers without germline mutations in BRCA1/2: phase 2 EMBRACE trial.British journal of cancer · 2026Trial
- Non-parametric differential methylation analysis characterizes histotype-specific promoter regions in epithelial ovarian cancer.Epigenetics · 2026Article
- DNA methylation biomarkers for early detection of ovarian cancer.Molecular biology reports · 2026Review
- Genome-wide DNA methylation profiling of triple-negative breast cancer uncovers epigenetic biomarkers of tumor identity and the immune microenvironment.NPJ breast cancer · 2026Article
- Homologous recombination deficiency (HRD) testing of high-grade serous carcinoma using cytological samples.BJC reports · 2026Article
- PARP Inhibitor Sensitivity in Tumors Harboring Non-BRCA Homologous Recombination Gene Alterations: Current Evidence Across Ovarian, Breast, Prostate, and Pancreatic Cancers.International journal of molecular sciences · 2026Review
- Evaluation of NID2 and CDO1 methylation for ovarian cancer screening.Oncology letters · 2026Article
- Article
- Targeting epigenetic methylation: emerging diagnosis and therapeutic strategies in cancer.Experimental hematology & oncology · 2026Review
- High-Grade Serous Ovarian Carcinoma in the Genomics Era: Current Applications, Challenges and Future Directions.International journal of molecular sciences · 2026Review
- The Effects ofCells · 2026Article
- Breast Cancer Disparities in African and African-Ancestry Populations: Genetics, Epigenetics, Structural Barriers and Technology-Enabled Solutions.British journal of biomedical science · 2026Review
- Microbial metabolite 5-formamidoimidazole-4-carboxamide ribotide targets METTL1 to inhibit m7G modification of BRCA1 mRNA to inhibit high-grade serous ovarian cancer.Molecular medicine (Cambridge, Mass.) · 2025Article
- Decoding BRCA1 promoter hypermethylation: a new frontier in understanding sporadic breast cancer.Cancer gene therapy · 2025Article
- Epigenetic Factors in Pathogenesis of Retinoblastoma: DNA Methylation and Histone Acetylation.Current issues in molecular biology · 2025Review
- The Expression and Clinical Significance of C1orf106 in Low-Grade Serous Ovarian Cancer.The journal of obstetrics and gynaecology research · 2025Article
- BRCA1/2 methylation and expression dynamics in hereditary breast and ovarian cancer: insights from gene, protein, and TCGA analysis.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Article
- A Novel Droplet Digital PCR Assay for BRCA1 and RAD51C Methylation: Advancing Homologous Recombination Deficiency Detection in Ovarian Cancer.The Journal of molecular diagnostics : JMD · 2025Article
- BRCA1 promoter methylation predicts PARPi response in ovarian cancer: insights from the KOMET study.Clinical epigenetics · 2025Article
- CG>TG mutation frequency as negative predictor of homologous recombination deficiency in ovarian and breast cancer.Communications biology · 2025Article
Corrections and comments
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Authors and funding
34 authors at 20 institutions in 9 countries.
Funding
Abstract
backgroundBRCA1 methylation has been associated with homologous recombination deficiency, a biomarker of platinum sensitivity. Studies evaluating BRCA1-methylated tubal and ovarian cancer (OC) do not consistently support improved survival following platinum chemotherapy. We examine the characteristics of BRCA1-methylated OC in a meta-analysis of individual participant data.
methodsData of 2636 participants across 15 studies were analyzed. BRCA1-methylated tumors were defined according to their original study. Associations between BRCA1 methylation and clinicopathological characteristics were evaluated. The effects of methylation on overall survival (OS) and progression-free survival (PFS) were examined using mixed-effects models. All statistical tests were 2-sided.
results430 (16.3%) tumors were BRCA1-methylated. BRCA1 methylation was associated with younger age and advanced-stage, high-grade serous OC. There were no survival differences between BRCA1-methylated and non-BRCA1-methylated OC (median PFS = 20.0 vs 18.5 months, hazard ratio [HR] = 1.01, 95% CI = 0.87 to 1.16; P = .98; median OS = 46.6 vs 48.0 months, HR = 1.02, 95% CI = 0.87 to 1.18; P = .96). Where BRCA1/2 mutations were evaluated (n = 1248), BRCA1 methylation displayed no survival advantage over BRCA1/2-intact (BRCA1/2 wild-type non-BRCA1-methylated) OC. Studies used different methods to define BRCA1 methylation. Where BRCA1 methylation was determined using methylation-specific polymerase chain reaction and gel electrophoresis (n = 834), it was associated with improved survival (PFS: HR = 0.80, 95% CI = 0.66 to 0.97; P = .02; OS: HR = 0.80, 95% CI = 0.63 to 1.00; P = .05) on mixed-effects modeling.
conclusionBRCA1-methylated OC displays similar clinicopathological features to BRCA1-mutated OC but is not associated with survival. Heterogeneity within BRCA1 methylation assays influences associations. Refining these assays may better identify cases with silenced BRCA1 function and improved patient outcomes.
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