ArticleInternational journal of cancer2018
Single CpG hypermethylation, allele methylation errors, and decreased expression of multiple tumor suppressor genes in normal body cells of mutation-negative early-onset and high-risk breast cancer patients.
Article in International journal of cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 21 citations in OpenAlex.
- BRCA1 promoter hypermethylation is not associated with germline variants in Polish breast cancer patients.Hereditary cancer in clinical practice · 2025Article
- Impact of anthracycline-based chemotherapy on RB1 gene methylation in peripheral blood leukocytes and biomarkers of oxidative stress and inflammation in sarcoma patients.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Article
- PTEN promoter methylation predicts 10-year prognosis in hormone receptor-positive early breast cancer patients who received adjuvant tamoxifen endocrine therapy.Breast cancer research and treatment · 2022Article
- Hypermethylation ofEXCLI journal · 2022Article
- AIM2 deficiency in B cells ameliorates systemic lupus erythematosus by regulating Blimp-1-Bcl-6 axis-mediated B-cell differentiation.Signal transduction and targeted therapy · 2021Article
- Methylation of the Promoter Region of the Tight Junction Protein-1 by DNMT1 Induces EMT-like Features in Multiple Myeloma.Molecular therapy oncolytics · 2020Article
- circIQCH sponges miR-145 to promote breast cancer progression by upregulating DNMT3A expression.Aging · 2020Article
- Article
- High-Resolution Bisulfite-Sequencing of Peripheral Blood DNA Methylation in Early-Onset and Familial Risk Breast Cancer Patients.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- Clinical significance of aberrant DEUP1 promoter methylation in hepatocellular carcinoma.Oncology letters · 2019Article
- ConstitutiveCancers · 2019Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To evaluate the role of constitutive epigenetic changes in normal body cells of BRCA1/BRCA2-mutation negative patients, we have developed a deep bisulfite sequencing assay targeting the promoter regions of 8 tumor suppressor (TS) genes (BRCA1, BRCA2, RAD51C, ATM, PTEN, TP53, MLH1, RB1) and the estrogene receptor gene (ESR1), which plays a role in tumor progression. We analyzed blood samples of two breast cancer (BC) cohorts with early onset (EO) and high risk (HR) for a heterozygous mutation, respectively, along with age-matched controls. Methylation analysis of up to 50,000 individual DNA molecules per gene and sample allowed quantification of epimutations (alleles with >50% methylated CpGs), which are associated with epigenetic silencing. Compared to ESR1, which is representative for an average promoter, TS genes were characterized by a very low (< 1%) average methylation level and a very low mean epimutation rate (EMR; < 0.0001% to 0.1%). With exception of BRCA1, which showed an increased EMR in BC (0.31% vs. 0.06%), there was no significant difference between patients and controls. One of 36 HR BC patients exhibited a dramatically increased EMR (14.7%) in BRCA1, consistent with a disease-causing epimutation. Approximately one third (15 of 44) EO BC patients exhibited increased rates of single CpG methylation errors in multiple TS genes. Both EO and HR BC patients exhibited global underexpression of blood TS genes. We propose that epigenetic abnormalities in normal body cells are indicative of disturbed mechanisms for maintaining low methylation and appropriate expression levels and may be associated with an increased BC risk.
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