Homologous recombination deficiency among patients with germline or somatic non-BRCA1/2 homologous recombination repair gene variations

作者：Yue Li, Xinhua Yang, Haoyang Cai, Fang Wang · 发表于：npj Precision Oncology · 年份：2025 · DOI：10.1038/s41698-025-00999-2 · 被引用次数：11 · 研究领域：CRISPR and Genetic Engineering、DNA Repair Mechanisms、PARP inhibition in cancer therapy

This study examined the relationship between homologous recombination deficiency (HRD) and variations in non-BRCA1/2 homologous recombination repair (HRR) genes. 27.3% (132/483) of the patients with ovarian, breast, endometrial, prostate, and pancreatic cancers carrying non-BRCA1/2 HRR variations were HRD + . Germline mutations were associated with significantly higher HRD+ rates than somatic mutations, while biallelic alterations did not show stronger associations with HRD compared to monoallelic alterations. High HRD+ rates (66.7-100.0%) were associated with variations in PALB2, RAD51C/D, and RAD54L, while low HRD+ rates (0-37.5%) corresponded with variations in PTEN, ATM, BRIP1, CDK12, and NBN, which may be influenced by variation grade and tissue origin. HRD positivity was mutually exclusive with HER2+ status in breast cancer and with TMB-H/MSI-H in endometrial cancer. Overall, these findings highlight the different strengths of the correlation between non-BRCA1/2 HRR gene variations and HRD and guide HRD testing in cases of "BRCA1/2-wildtype" results.