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Keywords: F1LCDx, ctDNA, coverage, analytical validation performance, tumor types
Liquid-based biopsies using the circulating cell-free DNA (cfDNA) have been developed rapidly and have become an alternative to overcome some of the challenges of tissue-based biopsies. One of the challenges for liquid-based biopsies is that the blood sample selection is limited by sample cfDNA yield compared to tissue-based biopsies, and this becomes even more challenging for rare biomarkers. Given that the circulating tumor DNA (ctDNA) being detected is shed away from the tumor and into the blood for liquid-based biopsies, it is expected that differences in test performance that could arise from the tumor tissue milieu will not be present in ctDNA, and the liquid-based biopsy does not suffer the same procurement differences as tissue-based biopsies, we hypothesized that for Foundation Medicine, Inc (FMI)’s FDA-approved liquid biopsy, FoundationOne®Liquid CDx (F1LCDx) assay, a pan-cancer cfDNA-based comprehensive genomic profiling assay, extracted DNA arising from any tumor type would have the same performance with regards to coverage metrics as well as analytical validation performance (i.e., in-process and post-sequencing QC metrics, precision, and concordance) as extracted DNA from any other tumor type. The assessment included >200,000 unique short variants across >300 genes and >300 raw disease ontologies across >31,000 patients’ samples. The results showed comparable coverage metrics distribution between tumor types with samples from the FMI clinical commercial database, and small pairwise differences (<7%) in pass rates for each step of in-process and post-sequencing QC, in mean reproducibility and mean repeatability, in variant-level positive percent agreement and negative percent agreement between tumor types. Overall, these results demonstrate the comparable performance for DNA extracted in different tumor types for the F1LCDx assay.