ArticleHuman molecular genetics2012
Constitutive promoter methylation of BRCA1 and RAD51C in patients with familial ovarian cancer and early-onset sporadic breast cancer.
Article in Human molecular genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 1 of them a synthesis that pooled it.
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Who cites it
65 citing papers in PubMed, 1 synthesis or guideline pooled it, 140 citations in OpenAlex.
- BRIP1, RAD51C, and RAD51D mutations are associated with high susceptibility to ovarian cancer: mutation prevalence and precise risk estimates based on a pooled analysis of ~30,000 cases.Journal of ovarian research · 2020Pooled it
- The Effects ofCells · 2026Article
- Constitutional epimutations in LTBP4, a component of the TGF-β signaling, and in BRCA1, as potential drivers of early-onset colorectal cancer.Clinical epigenetics · 2025Article
- BRCA1 promoter hypermethylation is not associated with germline variants in Polish breast cancer patients.Hereditary cancer in clinical practice · 2025Article
- Constitutional Epimutations: From Rare Events Toward Major Cancer Risk Factors?JCO precision oncology · 2025Review
- Triple-Negative Breast Cancer on the Rise or…? [Letter].Breast cancer (Dove Medical Press) · 2025Article
- Long-read sequencing of an advanced cancer cohort resolves rearrangements, unravels haplotypes, and reveals methylation landscapes.Cell genomics · 2024Article
- High-level tumour methylation ofNAR cancer · 2024Article
- Methylation marks in blood DNA reveal breast cancer risk in patients fulfilling hereditary disease criteria.NPJ precision oncology · 2024Article
- ConstitutionalHuman mutation · 2024Review
- Unraveling noncoding DNA variants and epimutations: a paradigm shift in hereditary cancer research.Future oncology (London, England) · 2024Review
- Prenatal BRCA1 epimutations contribute significantly to triple-negative breast cancer development.Genome medicine · 2023Article
- Genomic Profiling Reveals Germline Predisposition and Homologous Recombination Deficiency in Pancreatic Acinar Cell Carcinoma.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2023Article
- Contribution of constitutional BRCA1 promoter methylation to early-onset and familial breast cancer patients from Pakistan.Breast cancer research and treatment · 2023Article
- Analytical sensitivity of a method is critical in detection of low-level BRCA1 constitutional epimutation.Scientific reports · 2023Article
- Identifying primary and secondary MLH1 epimutation carriers displaying low-level constitutional MLH1 methylation using droplet digital PCR and genome-wide DNA methylation profiling of colorectal cancers.Clinical epigenetics · 2023Article
- Article
- Evaluation of genetic alterations in hereditary cancer susceptibility genes in the Ashkenazi Jewish women community of Mexico.Frontiers in genetics · 2023Article
- Methylation of promoter region of BRCA1 gene versus pathogenic variants of gene: risk factor or clinical marker of breast cancer.Breast cancer research and treatment · 2022Article
- Constitutional BRCA1 Methylation and Risk of Incident Triple-Negative Breast Cancer and High-grade Serous Ovarian Cancer.JAMA oncology · 2022Article
5 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Genetic defects in breast cancer (BC) susceptibility genes, most importantly BRCA1 and BRCA2, account for ~40% of hereditary BC and ovarian cancer (OC). Little is known about the contribution of constitutive (soma-wide) epimutations to the remaining cases. We developed bisulfite pyrosequencing assays to screen >600 affected BRCA1/BRCA2 mutation-negative patients from the German Consortium for Hereditary Breast and Ovarian Cancer for constitutive hypermethylation of ATM, BRCA1, BRCA2, RAD51C, PTEN and TP53 in blood cells. In a second step, patients with ≥6% promoter methylation were analyzed by bisulfite plasmid sequencing to demonstrate the presence of hypermethylated alleles (epimutations), indicative of epigenetic gene silencing. Altogether we identified nine (1.4%) patients with constitutive BRCA1 and three (0.5%) with RAD51C hypermethylation. Epimutations were found in both sporadic cases, in particular in 2 (5.5%) of 37 patients with early-onset BC, and familial cases, in particular 4 (10%) of 39 patients with OC. Hypermethylation was always confined to one of the two parental alleles in a subset (12-40%) of the analyzed cells. Because epimutations occurred in cell types from different embryonal layers, they most likely originated in single cells during early somatic development. We propose that analogous to germline genetic mutations constitutive epimutations may serve as the first hit of tumor development. Because the role of constitutive epimutations in cancer development is likely to be largely underestimated, future strategies for effective testing of susceptibility to BC and OC should include an epimutation screen.
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