Breast Cancer Research (May 2021)

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

  • 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

DOI
https://doi.org/10.1186/s13058-021-01428-5
Journal volume & issue
Vol. 23, no. 1
pp. 1 – 7

Abstract

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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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