Tumor Genomic Profiling Reports from Different Vendors: A Comparisonwith Respect to Clinical Action Ability of the Provided Data

Background: Next generation sequencing (NGS) of selected genes is an expanding field of solid tumor characterization. Multiple vendors offer this service, but panel design and policies on interpretive reporting are variable. This study compared reports from selected vendors, with emphasis on clinical Action ability reporting. Methodology: DNA aliquots of five breast and five colorectal cancers were sent to providers offering the following solid tumor NGS tests: Foundation oneTM, StrandAdvantageTM, CANCP, and GeneTrailsTM. The interpretive reports were compared for the reporting of clinically actionable variants. Results: Detection of mutants was mostly consistent (17 of 21, 81% concordant), while detection of copy number variants was highly discordant (6 of 23, 26.1% concordant). Discordance of copy number variation appeared to be primarily due to difference in analytical sensitivity. Actionable variants with approved targeted therapies for the same tumor type were detected and interpreted uniformly by all tests. Reporting of variants with other action ability was variable, largely due to difference in panel design and analytical sensitivity, and, to a lesser degree, to different annotation policies. Actionable variant reporting by Foundation one provided better coverage of clinical trials for targeted therapies while strand advantage uniquely covered chemotherapeutic response modulation. GeneTrails provided moderate coverage of clinical trials despite its small gene panel size. Utility of rearrangement targets in Foundation one and StrandAdvantage panel was not evident, due to the tumor type assessed. Conclusion: All enrolled tests reported actionable variants with FDA-approved target therapy for the specific tumor type with consistent clinical interpretations. In contrast, reporting of variants with other Action ability was heavily impacted by panel design, reporting policy, and annotation policy. Larger studies will be needed to quantify the qualitative differences outlined above and evaluate the benefit to the patient in order to improve the practice of precision medicine in the future.