High prevalence of constitutional BRCA1 epimutation in patients with early-onset triple-negative breast cancer
Abstract Between 5 and 8% of the general population carry a constitutional methylation of the BRCA1 promoter (“epimutation”). Several studies have suggested that these BRCA1 epimutations confer an increased risk of breast cancer, in particular triple-negative breast cancer (TNBC), with an earlier on...
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| Format: | Article |
| Language: | English |
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BMC
2025-06-01
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| Series: | Clinical Epigenetics |
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| Online Access: | https://doi.org/10.1186/s13148-025-01885-1 |
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| author | Mathias Schwartz Sabrina Ibadioune Hélène Delhomelle Solenn Barraud Sandrine M. Caputo Olfa Trabelsi-Grati Marie-Charlotte Villy Anthony Laugé Roseline Tang Etienne Rouleau Emmanuelle Mouret-Fourme Dominique Stoppa-Lyonnet Éric Pasmant Lisa Golmard Chrystelle Colas Ivan Bièche |
| author_facet | Mathias Schwartz Sabrina Ibadioune Hélène Delhomelle Solenn Barraud Sandrine M. Caputo Olfa Trabelsi-Grati Marie-Charlotte Villy Anthony Laugé Roseline Tang Etienne Rouleau Emmanuelle Mouret-Fourme Dominique Stoppa-Lyonnet Éric Pasmant Lisa Golmard Chrystelle Colas Ivan Bièche |
| author_sort | Mathias Schwartz |
| collection | DOAJ |
| description | Abstract Between 5 and 8% of the general population carry a constitutional methylation of the BRCA1 promoter (“epimutation”). Several studies have suggested that these BRCA1 epimutations confer an increased risk of breast cancer, in particular triple-negative breast cancer (TNBC), with an earlier onset than in the general population. However, those studies relied on very few patients with early-onset TNBC. Using specific Methylation-Sensitive High-Resolution Melting, we assessed BRCA1 epimutation prevalence in a large cohort of 112 early-onset (≤ 30 years-old) TNBC patients with no genetic cancer-predisposing pathogenic variants (PVs). We compared this cohort to 87 early-onset TNBC patients carrying cancer-predisposing PVs and to 93 late-onset (≥ 70 years-old) TNBC with no cancer-predisposing PVs. We observed a high prevalence of BRCA1 epimutation in blood cells from early-onset TNBC patients with no cancer-predisposing PVs (38/112, 33.9% [95% confidence interval: 25.4–43.6%]) as compared to early-onset patients with cancer-predisposing PVs (1/87, 1.1% [0.1–7.1%], p value < 0.001) and late-onset patients (11/93, 11.8% [6.3–20.6%], p value < 0.001). These differences remained significant when restricting to epimutations with low variant epiallele frequencies (VEF under 1%). Our results highlight the role of constitutional BRCA1 epimutations in early-onset TNBC risk and call for their integration into multifactorial models used to compute personalized breast cancer risk. |
| format | Article |
| id | doaj-art-e303b27e55094aec90ad74aefa2b2f6a |
| institution | OA Journals |
| issn | 1868-7083 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Clinical Epigenetics |
| spelling | doaj-art-e303b27e55094aec90ad74aefa2b2f6a2025-08-20T02:30:42ZengBMCClinical Epigenetics1868-70832025-06-011711610.1186/s13148-025-01885-1High prevalence of constitutional BRCA1 epimutation in patients with early-onset triple-negative breast cancerMathias Schwartz0Sabrina Ibadioune1Hélène Delhomelle2Solenn Barraud3Sandrine M. Caputo4Olfa Trabelsi-Grati5Marie-Charlotte Villy6Anthony Laugé7Roseline Tang8Etienne Rouleau9Emmanuelle Mouret-Fourme10Dominique Stoppa-Lyonnet11Éric Pasmant12Lisa Golmard13Chrystelle Colas14Ivan Bièche15Department of Genetics, Curie InstituteDepartment of Genetics, Curie InstituteDepartment of Genetics, Curie InstituteDepartment of Genetics, Curie InstituteDepartment of Genetics, Curie InstituteDepartment of Genetics, Curie InstituteDepartment of Genetics, Curie InstituteDepartment of Genetics, Curie InstituteCancer Genetics Laboratory, Medical Biology and Pathology Department, Gustave-Roussy Cancer CampusCancer Genetics Laboratory, Medical Biology and Pathology Department, Gustave-Roussy Cancer CampusDepartment of Genetics, Curie InstituteDepartment of Genetics, Curie InstituteDepartment of Genetics, Curie InstituteDepartment of Genetics, Curie InstituteDepartment of Genetics, Curie InstituteDepartment of Genetics, Curie InstituteAbstract Between 5 and 8% of the general population carry a constitutional methylation of the BRCA1 promoter (“epimutation”). Several studies have suggested that these BRCA1 epimutations confer an increased risk of breast cancer, in particular triple-negative breast cancer (TNBC), with an earlier onset than in the general population. However, those studies relied on very few patients with early-onset TNBC. Using specific Methylation-Sensitive High-Resolution Melting, we assessed BRCA1 epimutation prevalence in a large cohort of 112 early-onset (≤ 30 years-old) TNBC patients with no genetic cancer-predisposing pathogenic variants (PVs). We compared this cohort to 87 early-onset TNBC patients carrying cancer-predisposing PVs and to 93 late-onset (≥ 70 years-old) TNBC with no cancer-predisposing PVs. We observed a high prevalence of BRCA1 epimutation in blood cells from early-onset TNBC patients with no cancer-predisposing PVs (38/112, 33.9% [95% confidence interval: 25.4–43.6%]) as compared to early-onset patients with cancer-predisposing PVs (1/87, 1.1% [0.1–7.1%], p value < 0.001) and late-onset patients (11/93, 11.8% [6.3–20.6%], p value < 0.001). These differences remained significant when restricting to epimutations with low variant epiallele frequencies (VEF under 1%). Our results highlight the role of constitutional BRCA1 epimutations in early-onset TNBC risk and call for their integration into multifactorial models used to compute personalized breast cancer risk.https://doi.org/10.1186/s13148-025-01885-1HBOCMethylationPromoterCancer predispositionEpimutationConstitutional epimutation |
| spellingShingle | Mathias Schwartz Sabrina Ibadioune Hélène Delhomelle Solenn Barraud Sandrine M. Caputo Olfa Trabelsi-Grati Marie-Charlotte Villy Anthony Laugé Roseline Tang Etienne Rouleau Emmanuelle Mouret-Fourme Dominique Stoppa-Lyonnet Éric Pasmant Lisa Golmard Chrystelle Colas Ivan Bièche High prevalence of constitutional BRCA1 epimutation in patients with early-onset triple-negative breast cancer Clinical Epigenetics HBOC Methylation Promoter Cancer predisposition Epimutation Constitutional epimutation |
| title | High prevalence of constitutional BRCA1 epimutation in patients with early-onset triple-negative breast cancer |
| title_full | High prevalence of constitutional BRCA1 epimutation in patients with early-onset triple-negative breast cancer |
| title_fullStr | High prevalence of constitutional BRCA1 epimutation in patients with early-onset triple-negative breast cancer |
| title_full_unstemmed | High prevalence of constitutional BRCA1 epimutation in patients with early-onset triple-negative breast cancer |
| title_short | High prevalence of constitutional BRCA1 epimutation in patients with early-onset triple-negative breast cancer |
| title_sort | high prevalence of constitutional brca1 epimutation in patients with early onset triple negative breast cancer |
| topic | HBOC Methylation Promoter Cancer predisposition Epimutation Constitutional epimutation |
| url | https://doi.org/10.1186/s13148-025-01885-1 |
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