Department of Oncology, Habib Bourguiba Hospital, University of Sfax, Sfax, Tunisia.
Center of Biotechnology of Sfax, University of Sfax, Sidi Mansour Street Km 6, BP 1177, 3038, Sfax, Tunisia.
Mol Biol Rep. 2020 Sep;47(9):6507-6516. doi: 10.1007/s11033-020-05703-0. Epub 2020 Sep 8.
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.
男性乳腺癌（MBC）是一种罕见且侵袭性的疾病，与遗传因素有关。BRCA1 和 BRCA2 的突变占所有 MBC 病例的 10%，这表明还涉及其他遗传因素。本研究的目的是在有家族史的突尼斯 MBC 患者中使用 Ampliseq BRCA 面板筛选整个 BRCA1 和 BRCA2 外显子。此外，我们对一名早发性 BRCA 阴性患者使用 TruSight One 测序面板进行了外显子组测序。我们发现，在 6 名 MBC 患者中，只有 1 名（MBC-F1）在 BRCA2 基因的外显子 2 中携带了一个新的移码突变（c.17-20delAAGA，p.Lys6Xfs），导致 BRCA2 蛋白只有 6 个氨基酸。我们在对外显子组测序数据应用了几个过滤步骤后，选择了 9 个罕见变体。在这些变体中，根据它们在乳腺癌发生中的作用，我们保留了 6 个候选基因（MSH5、DCC、ERBB3、NOTCH3、DIAPH1 和 DNAH11）。需要进一步的研究来证实这些选定基因与家族性 MBC 的关联。
