A scalable high-throughput targeted next-generation sequencing assay for comprehensive genomic profiling of solid tumors.

Autor: Conroy JM; Research and Development, OmniSeq Inc., Buffalo, New York, United States of America.; Research Support Services, Roswell Park Comprehensive Cancer Center, Buffalo, New York, United States of America., Pabla S; Bioinformatics, OmniSeq Inc., Buffalo, New York, United States of America., Glenn ST; Research and Development, OmniSeq Inc., Buffalo, New York, United States of America.; Laboratory Operations, OmniSeq Inc., Buffalo, New York, United States of America.; HemePath Molecular, Roswell Park Comprehensive Cancer Center, Buffalo, New York, United States of America., Seager RJ; Bioinformatics, OmniSeq Inc., Buffalo, New York, United States of America., Van Roey E; Bioinformatics, OmniSeq Inc., Buffalo, New York, United States of America., Gao S; Bioinformatics, OmniSeq Inc., Buffalo, New York, United States of America., Burgher B; Research and Development, OmniSeq Inc., Buffalo, New York, United States of America., Andreas J; Research and Development, OmniSeq Inc., Buffalo, New York, United States of America., Giamo V; Research and Development, OmniSeq Inc., Buffalo, New York, United States of America., Mallon M; Research and Development, OmniSeq Inc., Buffalo, New York, United States of America., Lee YH; Clinical Evidence Development, OmniSeq Inc., Buffalo, New York, United States of America., DePietro P; Clinical Evidence Development, OmniSeq Inc., Buffalo, New York, United States of America., Nesline M; Clinical Evidence Development, OmniSeq Inc., Buffalo, New York, United States of America., Wang Y; Information Technology, OmniSeq Inc., Buffalo, New York, United States of America., Lenzo FL; Research and Development, OmniSeq Inc., Buffalo, New York, United States of America., Klein R; Medical Affairs, OmniSeq Inc., Buffalo, New York, United States of America., Zhang S; Laboratory Operations, OmniSeq Inc., Buffalo, New York, United States of America.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2021 Dec 02; Vol. 16 (12), pp. e0260089. Date of Electronic Publication: 2021 Dec 02 (Print Publication: 2021).
DOI: 10.1371/journal.pone.0260089
Abstrakt: Timely and accurate identification of molecular alterations in solid tumors is essential for proper management of patients with advanced cancers. This has created a need for rapid, scalable comprehensive genomic profiling (CGP) systems that detect an increasing number of therapeutically-relevant variant types and molecular signatures. In this study, we assessed the analytical performance of the TruSight Oncology 500 High-Throughput assay for detection of somatic alterations from formalin-fixed paraffin-embedded tissue specimens. In parallel, we developed supporting software and automated sample preparation systems designed to process up to 70 clinical samples in a single NovaSeq 6000TM sequencing run with a turnaround time of <7 days from specimen receipt to report. The results demonstrate that the scalable assay accurately and reproducibly detects small variants, copy number alterations, microsatellite instability (MSI) and tumor mutational burden (TMB) from 40ng DNA, and multiple gene fusions, including known and unknown partners and splice variants from 20ng RNA. 717 tumor samples and reference materials with previously known alterations in 96 cancer-related genes were sequenced to evaluate assay performance. All variant classes were reliably detected at consistent and reportable variant allele percentages with >99% overall accuracy and precision. Our results demonstrate that the high-throughput CGP assay is a reliable method for accurate detection of molecular alterations in support of precision therapeutics in oncology. The supporting systems and scalable workflow allow for efficient interpretation and prompt reporting of hundreds of patient cancer genomes per week with excellent analytical performance.
Competing Interests: The authors have the following interests. At the time of this research JC, SP, SG, RJS, EVR, SG, BB, JA, VG, MM, YHL, PD, MN, YW, FL, RK and SZ were employed by OmniSeq, Inc., the funder of this study. In addition, JC, SP, SG, PD, MN, RK and SZ were minority OmniSeq shareholders. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.
Databáze: MEDLINE
Externí odkaz: