Male breast cancer: No evidence for mosaic BRCA1 promoter methylation involvement

Abstract

Breast cancers (BC) are rare in men and are often caused by constitutional predisposing factors. In women, mosaic BRCA1 promoter methylations (MBPM) are frequent events, detected in 4-8% of healthy subjects. This constitutional epimutation increases risk of early-onset and triple-negative BC. However, the role of MBPM in male BC predisposition has never been assessed. We screened 40 blood samples from men affected by BC, and performed extensive tumour analysis on MBPM-positive patients. We detected two patients carrying MBPM. Surprisingly, tumour analysis revealed that neither of these two male BCs were caused by the constitutional BRCA1 epimutations carried by the patients.

Keywords: Breast neoplasm; DNA methylation; Epigenomics; Genetic testing; HBOC syndrome; Homologous recombination.

Fig. 1

Study design and graphic representation of BRCA1 (NM_007294) promoter analysis. BRCA1-specific Methylation-Sensitive High-Resolution Melting (MS-HRM) analyse 6 CpGs located in core BRCA1 promoter, nearby transcription start site. Unmethylated CpGs are represented by empty circles, methylated CpGs are represented by black-filled circles.

Fig. 2

Pedigrees of the first reported men affected by breast cancer who carry mosaic BRCA1 promoter methylation. BRCA1 methylation levels are indicated. Breast cancer patients are shown in black. HRD: homologous recombination deficiency; LOH: loss of heterozygosity.