Identification of novel candidate genes by exome sequencing in Tunisian familial male breast cancer patients

Male Breast Cancer (MBC) is a rare and aggressive disease that is associated with genetic factors. Mutations inBRCA1 and BRCA2 account for 10% of all MBC cases suggesting that other genetic factors are involved. The aim of the present study is to screen wholeBRCA1andBRCA2exons using the Ampliseq BRCA panel in Tunisian MBC patients with family history. Furthermore, we performed exome sequencing using the TruSight One sequencing panel on an early onsetBRCAnegative patient. We showed that among the 6 MBC patients, only one (MBC-F1) harbored a novel frameshift mutation in exon 2 of theBRCA2gene (c.17-20delAAGA, p.Lys6Xfs) resulting in a short BRCA2 protein of only 6 amino-acids. We selected 9 rare variants after applying several filter steps on the exome sequencing data. Among these variants, and based on their role in breast carcinogenesis, we retained 6 candidate genes (MSH5, DCC, ERBB3, NOTCH3, DIAPH1,andDNAH11). Further studies are needed to confirm the association of the selected genes with family MBC.