Comprehensive next-generation sequencing (NGS) assays enable the identification of clinically relevant mutations, enhancing the capability for targeted therapeutic interventions. In addition, genomic alterations driving the oncogenic roadmap and leading to resistance mechanisms are reshaping precision oncology. We report the workflow and clinical and technical validation of the OncoIndx®NGS platform—a comprehensive genomic profiling (CGP)-based assay for pan-cancer investigation. We evaluated the concordance between the OncoIndx®test findings and clinically established hotspot detection using SeraSeq reference standards. OncoIndx is a hybridization capture-based NGS assay for the targeted deep sequencing of all exons and selected introns of 1080 cancer-related genes. We show the outcome in the form of tier I and tier II single nucleotide variants (SNVs), copy number alterations (CNAs), and specific gene fusions. OncoIndx®also informs genome-wide tumor mutational burden (TMB), microsatellite instability (MSI), homologous recombination deficiency (HRD), and genomic loss of heterozygosity (gLOH). A total of 63 samples were utilized for validation with reference standards, clinical samples, and orthogonal assessment for genomic alterations. In addition, 49 cross-laboratory samples were validated for microsatellite instability (MSI), and for the tumor mutation burden (TMB), 18 samples as reference standards, 6 cross-laboratory samples, and 29 TCGA samples were utilized. We show a maximum clinical sensitivity of 98% and a positive predictive value (PPV) of 100% for the clinically actionable genomic variants detected by the assay. In addition, we demonstrate analytical validation with the performance of the assay, limit of detection (LoD), precision, and orthogonal concordance for various types of SVs, CNAs, genomic rearrangements, and complex biomarkers like TMB, MSI, and HRD. The assay offers reliable genomic predictions with the high-precision detection of actionable variants, validated by established reference standards.
全面的下一代测序（NGS）检测技术能够识别临床相关突变，从而增强靶向治疗干预的能力。此外，驱动肿瘤发生路径并导致耐药机制的基因组改变正在重塑精准肿瘤学领域。本文报告了OncoIndx®NGS平台的工作流程及临床与技术验证——这是一种基于全面基因组分析（CGP）的泛癌种检测方法。我们通过SeraSeq参考标准评估了OncoIndx®检测结果与临床已确立的热点检测之间的一致性。OncoIndx是一种基于杂交捕获的NGS检测，用于对1080个癌症相关基因的所有外显子和选定内含子进行靶向深度测序。我们以I类和II类单核苷酸变异（SNVs）、拷贝数变异（CNAs）以及特定基因融合的形式展示了检测结果。OncoIndx®还能提供全基因组肿瘤突变负荷（TMB）、微卫星不稳定性（MSI）、同源重组缺陷（HRD）以及基因组杂合性缺失（gLOH）的信息。共使用63个样本进行验证，包括参考标准、临床样本以及对基因组改变的正交评估。此外，49个跨实验室样本用于微卫星不稳定性（MSI）验证，而针对肿瘤突变负荷（TMB），使用了18个参考标准样本、6个跨实验室样本和29个TCGA样本。我们展示了该检测方法对临床可操作基因组变异的最大临床灵敏度为98%，阳性预测值（PPV）为100%。此外，我们还通过检测性能、检测限（LoD）、精密度以及对各类结构变异（SVs）、拷贝数变异（CNAs）、基因组重排以及复杂生物标志物（如TMB、MSI和HRD）的正交一致性进行了分析验证。该检测方法通过已确立的参考标准验证，能够以高精度检测可操作变异，提供可靠的基因组预测。
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