Nguyen Hoang Thien-Phuc, Tran Nam H B, Nguyen Tien Anh, Ngo My T T, Doan Anh Duong, Nguyen Du Quyen, Tang Hung Sang, Nguyen Duy Sinh, Thi Cam Tu Nguyen, Thi Thanh Thuy Do, Nguyen Hoai-Nghia, Giang Hoa, Tu Lan N
Medical Genetics Institute, Ho Chi Minh, Vietnam.
Gene Solutions, Ho Chi Minh, Vietnam.
Front Oncol. 2025 Sep 1;15:1593881. doi: 10.3389/fonc.2025.1593881. eCollection 2025.
Assessing homologous recombination deficiency (HRD) has been recommended by clinical guidelines for patients with ovarian cancer (OC) as it predicts sensitivity to poly (ADP-ribose) polymerase inhibitors (PARPi). However, HRD testing is complex and either inaccessible or unaffordable for majority of OC patients in developing countries. Consequently, the prevalence of HRD in OC remains unknown.
We examined HRD status of 77 Vietnamese patients with OC using a new laboratory-developed test (HRD Insight, Gene Solutions). Tumor DNA was extracted from FFPE samples, followed by next-generation sequencing to detect deleterious or suspected deleterious variants in / genes. Shallow whole genome sequencing was performed to determine the whole Genomic Instability (wGI) score by assessing the presence of large-scale intra-chromosomal copy number alterations.
The assay was first benchmarked against commercial HRD kits including TruSight Oncology 500 HRD (Illumina), SOPHiA DDM HRD Solutions (Sophia Genetics) and HRD Focus Panel (AmoyDx), and showed an overall percent agreement of 90.0%, 96.3%, and 96.4% respectively. The successful rate of sequencing was 94.8% (73/77) and the prevalence of HRD in OC patients was 54.8% (40/73). mutations and positive wGI scores were found in 16.4% (12/73) and 47.9% (35/73) of the patients respectively. Among those with wild-type /, 40.5% of them had positive wGI scores and hence positive HRD. Age at diagnosis was not affected by both and wGI status.
HRD Insight assay could accurately and robustly determine the HRD status of ovarian tissue samples, including those with low quality.
临床指南已建议对卵巢癌（OC）患者进行同源重组缺陷（HRD）评估，因为它可预测对聚（ADP - 核糖）聚合酶抑制剂（PARPi）的敏感性。然而，HRD检测复杂，对于发展中国家的大多数OC患者来说，要么无法进行，要么费用高昂。因此，OC中HRD的患病率仍然未知。
我们使用一种新的实验室研发检测方法（HRD Insight，基因解决方案公司）检测了77例越南OC患者的HRD状态。从福尔马林固定石蜡包埋（FFPE）样本中提取肿瘤DNA，然后进行二代测序以检测/基因中的有害或疑似有害变异。通过评估大规模染色体内拷贝数改变的存在情况进行浅层全基因组测序，以确定全基因组不稳定性（wGI）评分。
该检测方法首先与商业HRD试剂盒进行比对，包括TruSight Oncology 500 HRD（Illumina公司）、SOPHiA DDM HRD解决方案（Sophia Genetics公司）和HRD Focus Panel（厦门艾德公司），总体一致性百分比分别为90.0%、96.3%和96.4%。测序成功率为94.8%（73/77），OC患者中HRD的患病率为54.8%（40/73）。分别在16.4%（12/73）和47.9%（35/73）的患者中发现了 突变和阳性wGI评分。在野生型/的患者中，40.5%的患者wGI评分为阳性，因此HRD为阳性。诊断时的年龄不受 和wGI状态的影响。
HRD Insight检测方法能够准确、可靠地确定卵巢组织样本的HRD状态，包括质量较低的样本。
