Laboratory of Epigenetics, Research Centre for Medical Genetics, Moskvorechie St., 1, 115522 Moscow, Russia.
Department of Pathology, Russian Medical Academy of Continuing Professional Education, 125993 Moscow, Russia.
Int J Mol Sci. 2023 Jun 22;24(13):10497. doi: 10.3390/ijms241310497.
Assessment of homologous recombination deficiency (HRD) status is now essential for ovarian cancer patient management. The aim of our study was to analyze the influence of ethnic variations, tumor purity, and neoadjuvant chemotherapy (CT) on the determination of HRD scores as well as to evaluate feasibility of HRD testing with the Amoy HRD Focus Assay in routine clinical practice. The HRD status, including the status and genomic scar score (GSS), was analyzed in 452 ovarian cancer specimens. The successful rate of HRD testing was 86% (388/452). The mutational rate was 29% (114/388); 252 samples (65%) were classified as HRD-positive. Our data demonstrate the feasibility of internal HRD testing by the AmoyDx HRD Focus Panel for high-grade serous ovarian cancer (HGSOC), showing results similar to other methods. The HRD rate in the Russian population is very similar to those of other European populations, as is the mutation frequency. The most substantial contribution to HRD level diversity is testing criteria depending on intrahospital arrangements. The analysis shows that biallelic alterations had higher GSS compared with those with monoallelic inactivation, consistent with positive HRD status. The study indicates that grades 1-2 of the pathological response caused by chemotherapy affect HRD scores and suggests controlling for tumor purity of 40% or more as a critical factor for GSS measurement.
同源重组缺陷（HRD）状态的评估现在是卵巢癌患者管理的必要条件。我们的研究目的是分析种族差异、肿瘤纯度和新辅助化疗（CT）对 HRD 评分的影响，以及评估 Amoy HRD Focus 检测在常规临床实践中检测 HRD 的可行性。分析了 452 个卵巢癌标本的 HRD 状态，包括 状态和基因组疤痕评分（GSS）。HRD 检测的成功率为 86%（388/452）。 突变率为 29%（114/388）；252 个样本（65%）被归类为 HRD 阳性。我们的数据证明了 AmoyDx HRD Focus 面板用于高级别浆液性卵巢癌（HGSOC）的内部 HRD 检测的可行性，结果与其他方法相似。俄罗斯人群的 HRD 率与其他欧洲人群非常相似， 突变频率也是如此。测试标准取决于医院内部安排，这是 HRD 水平多样性的最大贡献因素。分析表明，双等位基因 改变的 GSS 高于单等位基因失活，与阳性 HRD 状态一致。该研究表明，化疗引起的病理反应 1-2 级会影响 HRD 评分，并建议将肿瘤纯度控制在 40%以上作为 GSS 测量的关键因素。
