Lara Gutierrez Ariadna, Halbwedl Iris, Sauer Stefan, Regitnig Peter, Petru Edgar, Seeböck Rita, Schubert Susanne, Peternell Cornelia, Bodó Koppány, Prein Kurt, Kashofer Karl
Diagnostic and Research Institute of Pathology, Medical University of Graz, Graz, Austria.
Division of Gynaecology, Medical University of Graz, Graz, Austria.
J Mol Diagn. 2025 Jun;27(6):475-484. doi: 10.1016/j.jmoldx.2025.02.011. Epub 2025 Apr 4.
Genomic instability scars are markers for detecting homologous recombination deficiency (HRD) status in patients with ovarian cancer and predicting the response to poly (ADP-ribose) polymerase inhibitor treatment. Currently, only a few reliable and validated assays are available, with the Myriad myChoice CDx being the most commonly used commercial assay for genomic instability scar score determination. Given the need for a more straightforward, accessible, and reliable method for detecting genomic instability scars methods, in this work, we describe the feasibility of using the microarray OncoScan copy number variant assay and open-source software packages to quantify genomic instability scores, and the development of an open-access online platform for genomic instability score calculation. The laboratory-developed test accurately classified homologous recombination-proficient and recombination-deficient samples based on genomic instability scores derived from the OncoScan copy number variant assay. Internally evaluated genomic instability scores demonstrated a 92% overall agreement and a higher sample success rate compared with externally analyzed genomic instability scar scores. The availability of HRD determination has doubled the number of patients eligible for poly (ADP-ribose) polymerase therapy. The assay can be conveniently performed on individual samples, and the open-access online platform facilitates HRD determination without the need for specialized bioinformatics support.
基因组不稳定瘢痕是检测卵巢癌患者同源重组缺陷(HRD)状态以及预测其对聚(ADP - 核糖)聚合酶抑制剂治疗反应的标志物。目前,仅有少数可靠且经过验证的检测方法,其中Myriad myChoice CDx是最常用于确定基因组不稳定瘢痕评分的商业检测方法。鉴于需要一种更直接、可及且可靠的检测基因组不稳定瘢痕的方法,在本研究中,我们描述了使用微阵列OncoScan拷贝数变异检测和开源软件包来量化基因组不稳定评分的可行性,以及开发一个用于基因组不稳定评分计算的开放获取在线平台。实验室开发的检测方法基于从OncoScan拷贝数变异检测得出的基因组不稳定评分,准确地将同源重组 proficient和重组缺陷样本进行了分类。内部评估的基因组不稳定评分显示总体一致性为92%,与外部分析的基因组不稳定瘢痕评分相比,样本成功率更高。HRD检测的可用性使符合聚(ADP - 核糖)聚合酶治疗条件的患者数量增加了一倍。该检测可方便地在单个样本上进行,且开放获取的在线平台便于进行HRD检测,无需专门的生物信息学支持。