Functional analysis of BRCT missense mutations in BRCA1‑mutated Chinese Han familial breast cancer

Zhang,Hong; Li,Linsen; Wang,Yuxia; Yin,C.  Cameron; Xie,Yuntao; Liu,Xijuan; Ding,Huirong; Tian,Zhihua; Shen,Jing; He,Long; Xia,Miaoran; Ma,Xi; Wu,Lina

doi:10.3892/ol.2017.7003

Functional analysis of BRCT missense mutations in BRCA1‑mutated Chinese Han familial breast cancer

Authors:
- Hong Zhang
- Linsen Li
- Yuxia Wang
- C. Cameron Yin
- Yuntao Xie
- Xijuan Liu
- Huirong Ding
- Zhihua Tian
- Jing Shen
- Long He
- Miaoran Xia
- Xi Ma
- Lina Wu
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Affiliations: Central Laboratory, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, Beijing 100142, P.R. China, State Key Laboratory of Animal Nutrition, China Agricultural University, Beijing 100193, P.R. China, Breast Center, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, Beijing 100142, P.R. China, Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Published online on: September 19, 2017 https://doi.org/10.3892/ol.2017.7003
Pages: 5839-5844
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Breast cancer 1 (BRCA1) is one of the most common tumor suppressor genes in breast cancer. The BRCT domain of BRCA1 has been shown to have a critical role in tumor suppression. In a previous study, two de novo BRCT missense mutations of BRCA1, G1763V and L1786P were identified from Chinese females with familial breast cancer. In the present study, the function of these two novel mutations were assessed by bioinformatics analysis and a series of experiments investigating cell proliferation, cell cycle and chemotherapy combination. Although bioinformatics analysis indicated that the mutants may be deleterious, a series of experiments revealed that the two mutants significantly reduced the growth and increased cell apoptosis similar to the function of BRCA1 wild type. Furthermore, no synergistic effect between the Olaparib and BRCA1 mutation was noted on cell apoptosis. These results demonstrated that these two mutations did not affect the tumor suppressor function of BRCA1. It was concluded that not all BRCA1 missense mutations are pathogenic and that any new BRCA1 mutation should be assessed for its effect on the tumor suppressor function of BRCA1.

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