Comparison of 2 Commercially Available Next-Generation Sequencing Platforms in Oncology

Abstract

The growing use of next generation-sequencing to identify cancer-associated alterations as well as the increasing number of targeted drugs holds promise for better matching patients with cancer with effective therapies. The FoundationOne (F1; Foundation Medicine) test sequences clinical tumor samples to characterize the exons of 315 cancer-associated genes and introns from 28 genes involved in rearrangements. The Guardant360 (G360; Guardant Health) test uses cell-free circulating DNA from blood to sequence 70 genes. Both the F1 and G360 tests have high specificities (>99%) and somewhat lower sensitivities. 1,2 However, little is known about how different next-generation sequencing tests compare when used in the same patients with cancer. We compared reports from F1 and G360 testing in 9 patients from a community oncology practice to determine the level of concordance between the platforms. Methods | This study was approved by the University of Washington Institutional Review Board. Patients consented to the study, titled "A Tumor Crowd Modeling Platform for Patients with Cancer," via an online patient information statement. Nine patients (mean [SD] age, 61 [19] years; 2 men and 7 women) underwent both F1 and G360 testing from April 14, 2015, to January 30, 2016. Patient reports from results of F1 tumor and G360 circulating tumor DNA testing were examined to generate a list of all genomic alterations detected by either assay and to assess concordance between reports. Reports from results

Concordance of Genomic Alterations by Next-Generation Sequencing in Tumor Tissue versus Circulating Tumor DNA in Breast Cancer

“…This may indicate that variants detected in smaller quantities may only be present in areas that are missed by tissue biopsies and potentially more difficult to detect in blood biopsies. The association of VAF with concordance was also recently reported in a similar comparison between tissue and ctDNA biopsies in a sample of nine patients (43).…”

Tumor Cell–Free DNA Copy Number Instability Predicts Therapeutic Response to Immunotherapy

“…Genomic testing of representative tumor biopsies provides mutational status of known driver genes, but methods currently available are reported to be inconsistent (5)(6)(7). Sequential biopsies during therapy have been proposed to capture alterations in driver mutations occurring with selection pressures from systemic therapies (8), which is often contraindicated due to technical or safety issues and patient reluctance.…”

Synthetic Circulating Cell-free DNA as Quality Control Materials for Somatic Mutation Detection in Liquid Biopsy for Cancer

“…Mu et al (33 ) showed that 1.3% of the variants detected by NGS were revealed to be false-positives by Sanger sequencing. Other studies also reported discordant NGS results from different laboratories (34,35 ). The errors observed in our study demonstrated that it is essential to have suitable quality control materials to ensure that different assays generate comparable results.…”