• Background: The study investigated whether mosaic BRCA1 promoter methylations (MBPM) contribute to male breast cancer predisposition by screening 40 blood samples from affected male patients using Methylation-Sensitive High-Resolution Melting (MS-HRM) with the EpiMelt BRCA1 kit (Methyldetect), followed by extensive tumor analyses (targeted gene sequencing, loss of heterozygosity detection, and shallow whole-genome sequencing) in MBPM-positive cases.

• Key Finding: Two out of the 40 male breast cancer patients (5%) carried MBPM; however, subsequent tumor analyses revealed reduced methylation levels in tumor tissues compared to non-cancerous samples, no loss of heterozygosity at the BRCA1 locus, and an absence of homologous recombination deficiency (HRD) signatures, indicating that the tumors did not arise from the constitutional epimutations.

• Conclusion: The findings provide no evidence supporting the involvement of mosaic BRCA1 promoter methylation in male breast cancer predisposition, highlighting distinct molecular characteristics between male and female breast cancers regarding constitutional epimutations.

• Original Article & Authors: Published in The Breast, Vol. 73, 2024, 103620. Authored by Mathias Schwartz, Sabrina Ibadioune, Sophie Vacher, Marie-Charlotte Villy, Olfa Trabelsi-Grati, Jessica Le Gall, Sandrine M. Caputo, Hélène Delhomelle, Mathilde Warcoin, Virginie Moncoutier, Christine Bourneix, Nadia Boutry-Kryza, Antoine De Pauw, Marc-Henri Stern, Bruno Buecher, Emmanuelle Mouret-Fourme, Chrystelle Colas, Dominique Stoppa-Lyonnet, Julien Masliah-Planchon, Lisa Golmard, and Ivan Bièche from the Department of Genetics, Institut Curie, UMR3244, Paris Sciences & Lettres Research University, Université Paris Cité, and Inserm U830, Paris, France, along with Hospices Civils de Lyon, Lyon, France.

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