Related Experiment Video
Updated: May 16, 2026

Identifying the Effects of BRCA1 Mutations on Homologous Recombination using Cells that Express Endogenous Wild-type BRCA1
Published on: February 17, 2011
Impact of Typical Somatic Gene Mutation Characteristics on Homologous Recombination Deficiency in Breast Cancer
Jinsui Du1, Chenglong Duan1, Jiaqi Zhang1
1Department of Breast Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
Background:
Homologous recombination deficiency (HRD) is an important contributor to genomic instability in breast cancer. This study aimed to characterize the mutational landscape of HRD breast cancer in a Shaanxi cohort and explore its clinicogenomic and immune microenvironment characteristics.
Methods:
Gene mutation profiles were analyzed in 130 breast cancer patients, and HRD status were quantified using Genomic Scar Scores (GSS). Multivariate logistic regression was used to identify clinicogenomic factors associated with HRD status. Immunohistochemistry for AR, CD8, and FOXC1 was further performed in tumor samples from 20 triple-negative breast cancer patients with different mutation patterns to evaluate molecular subtype characteristics.
Results:
The most frequently mutated genes in HRD patients were TP53 (61 cases), BRCA (29 cases; BRCA1: 18, BRCA2: 11), and other genes such as FANCA, PTEN. Tumors harboring comutations of TP53 and BRCA exhibited significantly higher GSS compared with tumors without detectable somatic mutations (82.33 vs. 22.25, P < .001). Among HRD-related triple-negative breast cancer, tumors with germline BRCA mutations alone were predominantly classified as basal-like immunosuppressed, whereas TP53-mutated tumors were mainly immunomodulatory. Tumors with co-occurring germline BRCA and TP53 mutations demonstrated higher CD8⁺ T cell infiltration and were primarily classified as the immunomodulatory subtype.
Conclusions:
BRCA and TP53 represent the most common genomic alterations in HRD-associated breast cancer in this cohort. Co-occurring BRCA and TP53 mutations were associated with higher genomic instability and distinct immune-related subtype characteristics in triple-negative breast cancer, highlighting the molecular heterogeneity of HRD-associated tumors.
Related Concept Videos
Mismatch Repair
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
Mismatch Repair
Cancers Originate from Somatic Mutations in a Single Cell
Cancers Originate from Somatic Mutations in a Single Cell
Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
