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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 in BRCA1 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 whole BRCA1 and BRCA2 exons 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 onset BRCA negative patient. We showed that among the 6 MBC patients, only one (MBC-F1) harbored a novel frameshift mutation in exon 2 of the BRCA2 gene (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, and DNAH11). Further studies are needed to confirm the association of the selected genes with family MBC.

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The authors thank the patients involved in the study.


This work was supported by a grant of the CIC- Habib Bourguiba Hospital Sfax-Tunisia, (Centre d’Investigation Clinique) and the Tunisian Ministry of Higher Education and Research.

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Corresponding author

Correspondence to Raja Mokdad-Gargouri.

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The authors have no conflict of interest to declare.

Ethical approval

Written informed consents were obtained from all participants. Ethical approval according to the Declaration of Helsinki Principles was obtained from the biomedical ethics committee of University Hospital Habib Bourguiba of Sfax -Tunisia.

Informed consent

Informed consent was obtained from all patients included in the study. This study is approved by Ethic committee of University Hospitals of Sfax-Tunisia.

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Ben Kridis-Rejeb, W., Ben Ayed-Guerfali, D., Ammous-Boukhris, N. et al. Identification of novel candidate genes by exome sequencing in Tunisian familial male breast cancer patients. Mol Biol Rep 47, 6507–6516 (2020).

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  • BRCA1
  • BRCA2
  • Male breast cancer
  • Candidate genes
  • Next generation sequencing
  • Panel-based exome sequencing