ArticleClinical cancer research : an official journal of the American Association for Cancer Research2023
Clinical Relevance of BRCA1 Promoter Methylation Testing in Patients with Ovarian Cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 37 citations in OpenAlex.
- Geneva Homologous Recombination Deficiency Test Is Predictive of Survival Benefit From Olaparib and Bevacizumab Maintenance in Ovarian Cancer.JCO precision oncology · 2025Trial
- Changes in Cyclin E1 expression and CCNE1 amplification in high-grade ovarian carcinomas post-PARP inhibitor exposure.British journal of cancer · 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
- HRR gene promoter methylation-guided nomogram predicts PARP inhibitor efficacy and progression-free survival in high-grade serous ovarian cancer.Clinical epigenetics · 2026Article
- Integrated Single-Cell Whole-Genome Sequencing and Spatial Transcriptomics Reveal Intratumoral Heterogeneity in Ovarian Cancer.Cancer research communications · 2026Article
- Immuno-molecular features associated with exceptional recurrence-free survivorship from Ovarian Cancer in the pre-PARP era.NPJ genomic medicine · 2026Article
- Clinical application of PARP inhibitors and emerging strategies to overcome resistance: a pan-cancer perspective.Biomarker research · 2026Review
- The Effects ofCells · 2026Article
- Homologous recombination deficiency correlates with tumor-infiltrating lymphocytes and predicts patient outcomes in hormone receptor-positive/HER2-negative breast cancer.Therapeutic advances in medical oncology · 2026Article
- Assessing the Detection Power of Genome-Wide Copy Number Variation Profiles in Prostate Cancer Using Simulated Shallow Whole-Genome Sequencing Data.JCO clinical cancer informatics · 2026Article
- Therapeutic targeting of post-translational modifications in ovarian cancer: mechanisms and clinical applications.Journal of ovarian research · 2025Review
- DNA Methylation in Ovarian and Endometrial Cancers: Predictive and Mechanistic Roles in PARP Inhibitor and ICI Response.Cancer science · 2025Review
- 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
- BRCA1 Promoter Methylation in Ovarian Cancer: Clinical Relevance and a Novel Diagnostic Approach Using Fragment Analysis.Cancer science · 2025Article
- High prevalence of constitutional BRCA1 epimutation in patients with early-onset triple-negative breast cancer.Clinical epigenetics · 2025Article
- A Rapid and Reliable Test forDiagnostics (Basel, Switzerland) · 2025Article
- Homologous recombination deficiency (HRD) testing landscape: clinical applications and technical validation for routine diagnostics.Biomarker research · 2025Review
- DNA Methylation in Prostate Cancer: Clinical Implications and Potential Applications.Cancer medicine · 2025Review
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Authors and funding
18 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeHomologous recombination deficiency (HRD) is closely related to PARP inhibitor (PARPi) benefit in ovarian cancer. The capacity of BRCA1 promoter methylation to predict prognosis and HRD status remains unclear. We aimed to correlate BRCA1 promoter methylation levels in patients with high-grade ovarian cancer to HRD status and clinical behavior to assess its clinical relevance. EXPERIMENTAL
designThis is a retrospective monocentric analysis of patients centrally tested for genomic instability score (GIS) by MyChoice CDx (Myriad Genetics). The detection of BRCA1 promoter methylation and quantification of methylation levels were performed by quantitative droplet digital PCR methodology. High BRCA1 methylation was defined as ≥70% and deemed to be associated with homozygous silencing.
resultsOf 100 patients, 11% harbored a deleterious BRCA1/2 mutation. GIS was considered positive (score ≥ 42) for 52 patients and negative for 48 patients. Using a 70% cutoff, 19% (15/79) of BRCA wild-type ovarian cancer had high BRCA1 methylation levels. All of the highly methylated tumors were classified as HRD, achieving a positive predictive value of 100%. We detected 14% (11/79) low-methylated tumors (1%-69%), and all of them were also classified as HRD. Mean GIS was 61.5 for BRCAmut, 66.4 for high-BRCAmeth, 58.9 for low-BRCAmeth, and 33.3 for BRCAwt unmethylated (P < 0.001). Low methylation levels detected in samples previously exposed to chemotherapy appeared to be associated with poor outcome post-platinum.
conclusionsPatients with ovarian cancer with high levels of BRCA1 hypermethylation are very likely to have high GIS and therefore represent good candidates for PARPi treatment. These results may be highly relevant to other tumor types for HRD prediction. See related commentary by Garg and Oza, p. 2957.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.