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01-12-2021 | Breast Cancer | Short report

Functional consequences of a rare missense BARD1 c.403G>A germline mutation identified in a triple-negative breast cancer patient

Authors: Yuanting Zheng, Bingying Li, Dejing Pan, Jun Cao, Jian Zhang, Xiaolin Wang, Xiangnan Li, Wanwan Hou, Ding Bao, Luyao Ren, Jingcheng Yang, Shangzi Wang, Yangyang Qiu, Fei Zhou, Zhiwei Liu, Sibo Zhu, Lei Zhang, Tao Qing, Yi Wang, Ying Yu, Jiaxue Wu, Xichun Hu, Leming Shi

Published in: Breast Cancer Research | Issue 1/2021

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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Title: Functional consequences of a rare missense BARD1 c.403G>A germline mutation identified in a triple-negative breast cancer patient
Authors: Yuanting Zheng
Bingying Li
Dejing Pan
Jun Cao
Jian Zhang
Xiaolin Wang
Xiangnan Li
Wanwan Hou
Ding Bao
Luyao Ren
Jingcheng Yang
Shangzi Wang
Yangyang Qiu
Fei Zhou
Zhiwei Liu
Sibo Zhu
Lei Zhang
Tao Qing
Yi Wang
Ying Yu
Jiaxue Wu
Xichun Hu
Leming Shi
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Breast Cancer
Breast Cancer
Published in: Breast Cancer Research / Issue 1/2021
Electronic ISSN: 1465-542X
DOI: https://doi.org/10.1186/s13058-021-01428-5

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