[Analysis of homologous recombination deficiency testing in ovarian cancer based on next-generation sequencing].

Authors

N M Li, H P Cheng, P Zhou, X H Li

Published in

Zhonghua zhong liu za zhi [Chinese journal of oncology]. Volume 48. Issue 7. Pages 924-932. Jul 23, 2026.

Abstract

Objective: To comprehensively evaluate homologous recombination deficiency (HRD) status via next-generation sequencing (NGS) in ovarian cancer patients and analyze its correlations with clinicopathological features, microsatellite instability (MSI), and tumor mutational burden (TMB), thereby providing evidence for genetic risk assessment, PARP inhibitor (PARPi)-targeted therapy, and prognostic management. Methods: A total of 182 ovarian cancer patients who underwent HRD testing in our department between January 2021 and August 2025 were enrolled. NGS was employed to detect germline and somatic mutations in BRCA1/2 and other genes, HRD scores, MSI, and TMB. HRD positivity was defined as the presence of a BRCA1/2 pathogenic/likely pathogenic mutation and/or a positive HRD score. Immunohistochemistry (IHC) was used to assess the expression of mismatch repair (MMR) protein and p53. Results: The overall HRD-positive rate was 65.38% (119/182), with an HRD score-positive rate of 53.30%. High-grade serous carcinoma (HGSC) constituted 84.62% (154/182) of cases and exhibited a significantly higher HRD-positive rate than those of other rare pathological subtypes [75.97% (117/154) vs. 7.14% (2/28), P＜0.001]. The BRCA mutation rate was 36.81% (67/182), with germline BRCA mutations accounting for 21.98% (40/182). Within the 119 HRD-positive patients, 56.30% harbored a BRCA mutation, 81.51% were HRD score-positive, and 43.70% were BRCA wild-type but HRD score-positive. Among other homologous recombination repair (HRR) genes, RAD51D had the highest mutation rate (12.64%, 23/182). A high concordance rate of 95.60% (174/182) was observed between p53 IHC results and TP53 mutational status, which reached 96.10% (148/154) in HGSC patients. In 167 patients, only one patient (0.60%) exhibited both MSI-high (H) and TMB-H, carrying a BRCA2 mutation and was HRD score-positive. TMB-H status was significantly associated with HRD positivity (P＜0.05), whereas no significant correlation was found between MSI status and HRD (P＞0.05). Conclusions: NGS enables a comprehensive and integrated assessment of HRD status in ovarian cancer. Our cohort revealed a high HRD-positive rate, particularly in HGSC. A substantial proportion of patients without BRCA mutations exhibited genomic instability, suggesting potential benefit from PARPi therapy. The correlation between HRD status and TMB features provides a rationale for exploring combination immunotherapy strategies.

PMID:
42477931
Bibliographic data and abstract were imported from PubMed on 21 Jul 2026.

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