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