Abstract 2938: Comprehensive genomic profiling of solid tumor patients with the OncoDEEP assay for broad analysis in clinical diagnostics
Authors: Speel Ernst-Jan M. , Volders Pieter-Jan , Van der Meulen Joni , De Cock Aaron , Vermeire Stefanie , Van Huysse Jacques , De Barsy Marie , Beniuga Gabriela , de Leng Wendy , Jansen Anne , Thijssen Sharon , Dubbink Hendrikus Jan , Ozgur Zeliha , van Ijcken Wilfred , Maes Brigitte , Froyen Guy 
Published: March 2024

Abstract
Somatic multi-gene analysis by Next Generation Sequencing (NGS) becomes standardly integrated in medical oncology for clinical decision making. However, with the fast-growing number of recommended and required genomic biomarkers, small panels have become vastly insufficient for most tumor types. Comprehensive Genomic Profiling (CGP) is amenable to screen for single nucleotide variants (SNVs) and subtle insertions and deletions (indels) in several hundreds of genes. Moreover, it provides information on copy number variations (CNVs) and gene fusions of the most relevant genes for optimal patient management. Currently, most comprehensive panels also allow for screening of tumor-agnostic genomic biomarkers, including microsatellite instability (MSI), tumor mutation burden (TMB) and homologous recombination deficiency (HRD), which are implemented as prognostic and therapeutic signatures in a wide variety of solid tumors. So far, only a handful of CGP assays have been validated for their diagnostic utility in routine laboratory practice for the care of cancer patients. In this study we report on an extensive multicentric analysis across multiple centers in Belgium and The Netherlands comparing the novel OncoDEEP CGP assay (OncoDNA) with the diagnostically validated TSO500 assay (Illumina). We describe the technical differences between both assays as well as their outcome and shortcomings. Detection of clinically relevant SNVs, indels and CNVs was very similar and differences were often due to assay-specific settings. Similarly, TMB, MSI and HRD data were concordant for most samples but those with scores close to the cut-offs could deviate. For fusion detection, concordance was found for the limited number of 11 clinically-actionable driver genes covered by the OncoDEEP kit. The uniformity of coverage was much higher with the OncoDEEP assay thereby allowing to pool 2- to 3-times more samples per NGS run. For the diagnostic implementation of the OncoDEEP assay we then performed an extensive validation with clinical samples representing a wide variety of solid tumor types, as well as reference samples. All performance metrics passed the validation criteria. In conclusion, the OncoDEEP kit can be used for reliable diagnostic comprehensive profiling of solid tumors, but currently, extensive fusion analysis requires an additional screening method.
Citation Format: Ernst-Jan M. Speel, Pieter-Jan Volders, Joni Van der Meulen, Aaron De Cock, Stefanie Vermeire, Jacques Van Huysse, Marie De Barsy, Gabriela Beniuga, Wendy de Leng, Anne Jansen, Sharon Thijssen, Hendrikus Jan Dubbink, Zeliha Ozgur, Wilfred van Ijcken, Brigitte Maes, Guy Froyen. Comprehensive genomic profiling of solid tumor patients with the OncoDEEP assay for broad analysis in clinical diagnostics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2938.