TY - JOUR
T1 - Identification of novel candidate genes by exome sequencing in Tunisian familial male breast cancer patients
AU - Ben Kridis-Rejeb, Wala
AU - Ben Ayed-Guerfali, Dorra
AU - Ammous-Boukhris, Nihel
AU - Ayadi, Wajdi
AU - Kifagi, Chamseddine
AU - Charfi, Slim
AU - Saguem, Ines
AU - Sellami-Boudawara, Tahia
AU - Daoud, Jamel
AU - Khanfir, Afef
AU - Mokdad-Gargouri, Raja
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
KW - BRCA1
KW - BRCA2
KW - Male breast cancer
KW - Candidate genes
KW - Next generation sequencing
KW - Panel-based exome sequencing
U2 - 10.1007/s11033-020-05703-0
DO - 10.1007/s11033-020-05703-0
M3 - Journal article
C2 - 32901360
SN - 0301-4851
VL - 47
SP - 6507
EP - 6516
JO - Molecular Biology Reports
JF - Molecular Biology Reports
IS - 9
ER -