C. Dumur, R. Krishnan, J. Almenara, K. Brown, Kailyn R. Dugan, Christiana Farni, Fatima Z. Ibrahim, Naomi A. Sanchez, Sumra Rathore, D. Pradhan, J. H. Hughes
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引用次数: 1
摘要
驱动癌变异体的检测和最近肿瘤不可知基因组生物标志物的鉴定推动了综合基因组谱分析(CGP)在疾病诊断、预后和治疗选择中的应用。Oncomine™Comprehensive Assay Plus (OCA+)面板使用DNA和RNA检测501个基因的单核苷酸变异(snv)、小插入/缺失(Indels)和结构变异(SVs)。此外,微卫星不稳定性(MSI)、肿瘤突变负担(TMB)和同源重组缺陷(HRD)状态在单一工作流程中进行评估。在此,我们介绍了OCA+的分析验证和临床应用。通过使用商业标准物质,我们发现所有生物标记物都具有良好的分析灵敏度、特异性和精度。snv和Indels的检出限(LoD)均为4%,但位于均聚区域的Indels的检出限为10%。另外一组81个肿瘤样本(包括细胞学涂片)进行测序,以评估OCA+在不同肿瘤类型中的临床应用。在临床队列中,除了子宫内膜癌病例的MSI评估,与PCR和IHC相比,OCA+对所有生物标志物的准确性,敏感性和特异性均为100%,准确性为83%,敏感性为67%。该试验的准确性和稳健性验证支持OCA+在实体瘤CGP中的应用。
Analytical Validation and Clinical Utilization of the Oncomine Comprehensive Assay Plus Panel for Comprehensive Genomic Profiling in Solid Tumors
The detection of driver oncogenic variants and the recent identification of tumor-agnostic genomic biomarkers has driven the use of comprehensive genomic profiling (CGP) for disease diagnosis, prognosis, and treatment selection. The Oncomine™ Comprehensive Assay Plus (OCA+) panel uses DNA and RNA to detect single nucleotide variants (SNVs), small insertions/deletions (Indels), and structural variants (SVs) across 501 genes. Moreover, microsatellite instability (MSI), tumor mutational burden (TMB), and homologous recombination deficiency (HRD) status are assessed in a single workflow. Herein, we present the analytical validation and clinical utilization of OCA+. By using commercial reference materials, we found good analytical sensitivity, specificity, and precision for all biomarkers analyzed. The limit of detection (LoD) was validated for SNVs and Indels at 4%, except for Indels located in homopolymeric regions, where the LoD was 10%. An additional set of 81 tumor samples, including cytology smears, were sequenced to assess the clinical utility of the OCA+ across different tumor types. Among the clinical cohort, OCA+ demonstrated 100% accuracy, sensitivity, and specificity for all biomarkers analyzed, except for MSI assessment of endometrial cancer cases, where 83% accuracy and 67% sensitivity were achieved, compared to PCR and IHC. The validation of accuracy and robustness of this assay supports the OCA+’s utility for solid tumor CGP.