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Functional consequences of a rare missense BARD1 c.403G>A germline mutation identified in a triple-negative breast cancer patient.
Zheng, Yuanting; Li, Bingying; Pan, Dejing; Cao, Jun; Zhang, Jian; Wang, Xiaolin; Li, Xiangnan; Hou, Wanwan; Bao, Ding; Ren, Luyao; Yang, Jingcheng; Wang, Shangzi; Qiu, Yangyang; Zhou, Fei; Liu, Zhiwei; Zhu, Sibo; Zhang, Lei; Qing, Tao; Wang, Yi; Yu, Ying; Wu, Jiaxue; Hu, Xichun; Shi, Leming.
Affiliation
  • Zheng Y; State Key Laboratory of Genetic Engineering, School of Life Sciences and Shanghai Cancer Center, Fudan University, Shanghai, China.
  • Li B; State Key Laboratory of Genetic Engineering, School of Life Sciences and Shanghai Cancer Center, Fudan University, Shanghai, China.
  • Pan D; Cambridge-Suda Genomic Resource Center and Jiangsu Key Laboratory of Neuropsychiatric Diseases Research, Soochow University, Suzhou, China.
  • Cao J; Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
  • Zhang J; Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
  • Wang X; State Key Laboratory of Genetic Engineering, School of Life Sciences and Shanghai Cancer Center, Fudan University, Shanghai, China.
  • Li X; State Key Laboratory of Genetic Engineering, School of Life Sciences and Shanghai Cancer Center, Fudan University, Shanghai, China.
  • Hou W; State Key Laboratory of Genetic Engineering, School of Life Sciences and Shanghai Cancer Center, Fudan University, Shanghai, China.
  • Bao D; State Key Laboratory of Genetic Engineering, School of Life Sciences and Shanghai Cancer Center, Fudan University, Shanghai, China.
  • Ren L; State Key Laboratory of Genetic Engineering, School of Life Sciences and Shanghai Cancer Center, Fudan University, Shanghai, China.
  • Yang J; State Key Laboratory of Genetic Engineering, School of Life Sciences and Shanghai Cancer Center, Fudan University, Shanghai, China.
  • Wang S; State Key Laboratory of Genetic Engineering, School of Life Sciences and Shanghai Cancer Center, Fudan University, Shanghai, China.
  • Qiu Y; State Key Laboratory of Genetic Engineering, School of Life Sciences and Zhongshan Hospital, Fudan University, Shanghai, China.
  • Zhou F; Cambridge-Suda Genomic Resource Center and Jiangsu Key Laboratory of Neuropsychiatric Diseases Research, Soochow University, Suzhou, China.
  • Liu Z; Cambridge-Suda Genomic Resource Center and Jiangsu Key Laboratory of Neuropsychiatric Diseases Research, Soochow University, Suzhou, China.
  • Zhu S; State Key Laboratory of Genetic Engineering, School of Life Sciences and Shanghai Cancer Center, Fudan University, Shanghai, China.
  • Zhang L; State Key Laboratory of Genetic Engineering, School of Life Sciences and Shanghai Cancer Center, Fudan University, Shanghai, China.
  • Qing T; State Key Laboratory of Genetic Engineering, School of Life Sciences and Shanghai Cancer Center, Fudan University, Shanghai, China.
  • Wang Y; State Key Laboratory of Genetic Engineering, School of Life Sciences and Shanghai Cancer Center, Fudan University, Shanghai, China.
  • Yu Y; State Key Laboratory of Genetic Engineering, School of Life Sciences and Shanghai Cancer Center, Fudan University, Shanghai, China. ying_yu@fudan.edu.cn.
  • Wu J; State Key Laboratory of Genetic Engineering, School of Life Sciences and Zhongshan Hospital, Fudan University, Shanghai, China. jiaxue@fudan.edu.cn.
  • Hu X; Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China. huxichun2017@163.com.
  • Shi L; State Key Laboratory of Genetic Engineering, School of Life Sciences and Shanghai Cancer Center, Fudan University, Shanghai, China. lemingshi@fudan.edu.cn.
Breast Cancer Res ; 23(1): 53, 2021 05 01.
Article in En | MEDLINE | ID: mdl-33933153
ABSTRACT
We identified a rare missense germline mutation in BARD1 (c.403G>A or p.Asp135Asn) as pathogenic using integrated genomics and transcriptomics profiling of germline and tumor samples from an early-onset triple-negative breast cancer patient who later was administrated with a PARP inhibitor for 2 months. We demonstrated in cell and mouse models that, compared to the wild-type, (1) c.403G>A mutant cell lines were more sensitive to irradiation, a DNA damage agent, and a PARP inhibitor; (2) c.403G>A mutation inhibited interaction between BARD1 and RAD51 (but not BRCA1); and (3) c.403G>A mutant mice were hypersensitive to ionizing radiation. Our study shed lights on the clinical interpretation of rare germline mutations of BARD1.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Tumor Suppressor Proteins / Ubiquitin-Protein Ligases / Triple Negative Breast Neoplasms Limits: Animals / Female / Humans Language: En Journal: Breast Cancer Res Journal subject: NEOPLASIAS Year: 2021 Type: Article Affiliation country: China
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Tumor Suppressor Proteins / Ubiquitin-Protein Ligases / Triple Negative Breast Neoplasms Limits: Animals / Female / Humans Language: En Journal: Breast Cancer Res Journal subject: NEOPLASIAS Year: 2021 Type: Article Affiliation country: China