Analytical Validation and Clinical Utilization of the Oncomine Comprehensive Assay Plus Panel for Comprehensive Genomic Profiling in Solid Tumors

Abstract

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.