The Novel Pathogenic Mutation c.849dupT in BRCA2 Contributes to the Nonsense-Mediated mRNA Decay of BRCA2 in Familial Breast Cancer.
- Author:
Sanrong LI
1
;
Jing MA
;
Caiying HU
;
Xing ZHANG
;
Deyong XIAO
;
Lili HAO
;
Wenjun XIA
;
Jichun YANG
;
Ling HU
;
Xiaowei LIU
;
Minghui DONG
;
Duan MA
;
Rensheng LIU
Author Information
- Publication Type:Brief Communication
- Keywords: BRCA2 genes; Breast neoplasms; High-throughput nucleotide sequencing; Mutation; Nonsense mediated mRNA decay
- MeSH: Blotting, Western; BRCA2 Protein; Breast Neoplasms*; Breast*; Drug Resistance; Female; Fluorescent Antibody Technique; Genes, BRCA2; High-Throughput Nucleotide Sequencing; Humans; Mass Screening; Nonsense Mediated mRNA Decay*; Ovarian Neoplasms; Pedigree; Prostate; RNA, Messenger; Siblings
- From:Journal of Breast Cancer 2018;21(3):330-333
- CountryRepublic of Korea
- Language:English
- Abstract: In this study, we used next-generation sequencing methods to screen 300 individuals for BRCA1 and BRCA2. A novel mutation (c.849dupT) in BRCA2 was identified in a female patient and her unaffected brothers. This mutation leads to the truncation of BRCA2 functional domains. Moreover, BRCA2 mRNA expression levels in mutation carriers are significantly reduced compared to noncarriers. Immunofluorescence and western blot assays showed that this mutation resulted in reduced BRCA2 protein expression. Thus, we identified a novel mutation that damaged the function and expression of BRCA2 in a family with breast cancer history. The pedigree analysis suggested that this mutation is strongly associated with familial breast cancer. Genetic counsellors suggest that mutation carriers in this family undergo routine screening for breast cancer, as well as other malignancies, such as prostate and ovarian cancer. The effects of this BRCA2 mutation on drug resistance should be taken into consideration during treatment.
