ArticleGenome medicine2023
Prenatal BRCA1 epimutations contribute significantly to triple-negative breast cancer development.
Article in Genome medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 29 citations in OpenAlex.
- Estrogen receptor-positive, BRCA1-deficient breast cancer: BRCA1-epimutated tumors presenting a piece to the puzzle.Breast cancer research : BCR · 2026Review
- Article
- Prevalence ofJCO precision oncology · 2026Article
- Constitutional BRCA1 Methylation is associated with high level of tumoral BRCA1 methylation and homologous recombination deficiency in triple-negative breast cancer.NPJ breast cancer · 2026Article
- An Overview of Emerging Trends in Targeted Therapy of Triple-Negative Breast Cancer.International journal of breast cancer · 2026Review
- Decoding BRCA1 promoter hypermethylation: a new frontier in understanding sporadic breast cancer.Cancer gene therapy · 2025Article
- Reply to: "Comments on the paper 'Extensive epigenomic dysregulation is a hallmark of homologous recombination deficiency in triple-negative breast cancer' by Y. Chen et al."International journal of cancer · 2025Article
- Citrullinated ENO1 Vaccine Enhances PD-1 Blockade in Mice Implanted with Murine Triple-Negative Breast Cancer Cells.Vaccines · 2025Article
- BRCA1 promoter hypermethylation is not associated with germline variants in Polish breast cancer patients.Hereditary cancer in clinical practice · 2025Article
- High prevalence of constitutional BRCA1 epimutation in patients with early-onset triple-negative breast cancer.Clinical epigenetics · 2025Article
- Germline variants in CDKN2A wild-type melanoma prone families.Molecular oncology · 2025Article
- Aromatics from fossil fuels and breast cancer.iScience · 2025Review
- Clinical-genomic characteristics of homologous recombination deficiency (HRD) in breast cancer: application model for practice.European journal of medical research · 2025Article
- Constitutional Epimutations: From Rare Events Toward Major Cancer Risk Factors?JCO precision oncology · 2025Review
- The cardio-oncologic burden of breast cancer: molecular mechanisms and importance of preclinical models.Basic research in cardiology · 2025Review
- Letter to the Editor in response to paper "BRCA1 promoter methylation in triple-negative breast cancer……" by K Daster et al.Breast cancer research and treatment · 2025Article
- Analysis of methylation features associated with neoadjuvant efficacy in HER2-positive breast cancer.Frontiers in oncology · 2025Article
- Triple-Negative Breast Cancer on the Rise or…? [Letter].Breast cancer (Dove Medical Press) · 2025Article
- Epigenetic alterations in triple-negative breast cancer and their clinical implications for diagnosis and therapy.Journal of Cancer · 2025Review
- Sex differences in DNA methylation variations according to ART conception-evidence from the Norwegian mother, father, and child cohort study.Scientific reports · 2024Article
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Authors and funding
16 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNormal cell BRCA1 epimutations have been associated with increased risk of triple-negative breast cancer (TNBC). However, the fraction of TNBCs that may have BRCA1 epimutations as their underlying cause is unknown. Neither are the time of occurrence and the potential inheritance patterns of BRCA1 epimutations established.
methodsTo address these questions, we analyzed BRCA1 methylation status in breast cancer tissue and matched white blood cells (WBC) from 408 patients with 411 primary breast cancers, including 66 TNBCs, applying a highly sensitive sequencing assay, allowing allele-resolved methylation assessment. Furthermore, to assess the time of origin and the characteristics of normal cell BRCA1 methylation, we analyzed umbilical cord blood of 1260 newborn girls and 200 newborn boys. Finally, we assessed BRCA1 methylation status among 575 mothers and 531 fathers of girls with (n = 102) and without (n = 473) BRCA1 methylation.
resultsWe found concordant tumor and mosaic WBC BRCA1 epimutations in 10 out of 66 patients with TNBC and in four out of six patients with estrogen receptor (ER)-low expression (< 10%) tumors (combined: 14 out of 72; 19.4%; 95% CI 11.1-30.5). In contrast, we found concordant WBC and tumor methylation in only three out of 220 patients with 221 ER ≥ 10% tumors and zero out of 114 patients with 116 HER2-positive tumors. Intraindividually, BRCA1 epimutations affected the same allele in normal and tumor cells. Assessing BRCA1 methylation in umbilical WBCs from girls, we found mosaic, predominantly monoallelic BRCA1 epimutations, with qualitative features similar to those in adults, in 113/1260 (9.0%) of individuals, but no correlation to BRCA1 methylation status either in mothers or fathers. A significantly lower fraction of newborn boys carried BRCA1 methylation (9/200; 4.5%) as compared to girls (p = 0.038). Similarly, WBC BRCA1 methylation was found less common among fathers (16/531; 3.0%), as compared to mothers (46/575; 8.0%; p = 0.0003).
conclusionsOur findings suggest prenatal BRCA1 epimutations might be the underlying cause of around 20% of TNBC and low-ER expression breast cancers. Such constitutional mosaic BRCA1 methylation likely arise through gender-related mechanisms in utero, independent of Mendelian inheritance.
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