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

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.

Mosaic promoter methylation contribution in hereditary breast/ovarian cancer pedigrees.

Purpose: Mosaic promoter methylation (meth) increases the risk of early-onset breast cancer, triple-negative breast cancer and ovarian cancer. As mosaic meth are believed to occur de novo, their role in family breast/ovarian cancer has not been assessed.

Patients: Blood-derived DNA from 20 unrelated affected cases from families with aggregation of breast/ovarian cancer, but with no germline pathogenic variants in /, or , were screened by methylation-sensitive high-resolution melting.

Hereditary cancer predispositions: Comparison of multigene panel sequencing on fresh-frozen breast/ovarian tumor versus blood.

In breast or ovarian cancer (BC/OC) patients with evocative personal and/or family history, multigene panel sequencing is performed on blood to diagnose hereditary predispositions. Additionally, BRCA1/BRCA2 testing can be performed on tumor sample for therapeutic purpose. The accuracy of multigene panel tumor analysis on BC/OC to detect predisposing germline pathogenic variants (gPV) has not been precisely assessed.

germline pathogenic variants and epithelial ovarian cancer: causal or coincidental findings?

germline pathogenic variants result in predisposition to familial adenomatous polyposis and extraintestinal tumours such as desmoid fibromatosis, medulloblastomas and thyroid cancers. They have also been recently involved in ovarian microcystic stromal tumours. inactivation has been described at the tumour level in epithelial ovarian cancers (EOCs).

Classification of 101 BRCA1 and BRCA2 variants of uncertain significance by cosegregation study: A powerful approach.

Up to 80% of BRCA1 and BRCA2 genetic variants remain of uncertain clinical significance (VUSs). Only variants classified as pathogenic or likely pathogenic can guide breast and ovarian cancer prevention measures and treatment by PARP inhibitors. We report the first results of the ongoing French national COVAR (cosegregation variant) study, the aim of which is to classify BRCA1/2 VUSs.