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

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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088670/
https://www.ncbi.nlm.nih.gov/pubmed/33933153
http://dx.doi.org/10.1186/s13058-021-01428-5
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author 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
author_facet 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
author_sort Zheng, Yuanting
collection PubMed
description 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13058-021-01428-5.
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spelling pubmed-80886702021-05-03 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 Breast Cancer Res Short Report 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13058-021-01428-5. BioMed Central 2021-05-01 2021 /pmc/articles/PMC8088670/ /pubmed/33933153 http://dx.doi.org/10.1186/s13058-021-01428-5 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Short Report
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
Functional consequences of a rare missense BARD1 c.403G>A germline mutation identified in a triple-negative breast cancer patient
title Functional consequences of a rare missense BARD1 c.403G>A germline mutation identified in a triple-negative breast cancer patient
title_full Functional consequences of a rare missense BARD1 c.403G>A germline mutation identified in a triple-negative breast cancer patient
title_fullStr Functional consequences of a rare missense BARD1 c.403G>A germline mutation identified in a triple-negative breast cancer patient
title_full_unstemmed Functional consequences of a rare missense BARD1 c.403G>A germline mutation identified in a triple-negative breast cancer patient
title_short Functional consequences of a rare missense BARD1 c.403G>A germline mutation identified in a triple-negative breast cancer patient
title_sort functional consequences of a rare missense bard1 c.403g>a germline mutation identified in a triple-negative breast cancer patient
topic Short Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088670/
https://www.ncbi.nlm.nih.gov/pubmed/33933153
http://dx.doi.org/10.1186/s13058-021-01428-5
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