Samples from patients with AML show high concordance in detection of mutations by NGS at local institutions vs central laboratories

• Type of Material: Article
• Authors: Uma Borate, The Ohio State University, Columbus; Fei Yang, Oregon Health and Science University; Richard Press, Oregon Health and Science University; Amy S. Ruppert, The Ohio State University, Columbus; Dan Jones, The Ohio State University, Columbus; Sean Caruthers, The Ohio State University, Columbus; Weiqiang Zhao, The Ohio State University, Columbus; Jo-Anne Vergilio, Foundation Medicine Inc.; Dean C. Pavlick, Foundation Medicine Inc.; Luke Juckett, Foundation Medicine Inc.; Brianna Norris, Oregon Health and Science University; Taylor Bucy, Oregon Health and Science University; Amy Burd, Leukemia and Lymphoma Society; Eytan M. Stein, Memorial Sloan Kettering Cancer Center; Prapti Patel, The University of Texas Southwestern Medical Center; Maria R. Baer, University of Maryland, Baltimore; Wendy Stock, University of Chicago; Gary Schiller, University of California, Los Angeles; William Blum, Emory University; Tibor Kovacsovics, University of Utah, Salt Lake City; Mark Litzow, Mayo Clinic, Rochester; James Foran, Mayo Clinic, Jacksonville; Nyla A. Heerema, Ohio State University, Columbus; Leonard Rosenberg, Leukemia and Lymphoma Society; Sonja Marcus, Leukemia and Lymphoma Society; Ashely Yocum, Leukemia and Lymphoma Society; Mona Stefanos, Ohio State University, Columbus; Brian Druker, Oregon Health and Science University; John C. Byrd, University of Cincinnati; Ross L. Levine, Memorial Sloan Kettering Cancer Center; Alice Mims, Ohio State University, Columbus
• Language: English
• Date: 2023-07-19
• Publisher: The American Society of Hematology
• Publication Version: Final Published Version
• Copyright Statement: © 2023 by The American Society of Hematology.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): https://doi.org/10.1182/bloodadvances.2022009008
• Title of Journal or Parent Work: Blood Advances
• Volume: 7
• Issue: 20
• Start Page: 6048
• End Page: 6054
• Grant/Funding Information: The work reported in this manuscript was funded by the Leukemia & Lymphoma Society.; This work was supported by National Cancer Institute P01 CA108671 11 (R.L.L.).
• Keywords: Next-generation sequencing; Beat AML Master Trial; acute myeloid leukemia
• Research Categories: Health Sciences, Public Health; Health Sciences, Oncology

Abstract

Next-generation sequencing (NGS) to identify pathogenic mutations is an integral part of acute myeloid leukemia (AML) therapeutic decision-making. The concordance in identifying pathogenic mutations among different NGS platforms at different diagnostic laboratories has been studied in solid tumors but not in myeloid malignancies to date. To determine this interlaboratory concordance, we collected a total of 194 AML bone marrow or peripheral blood samples from newly diagnosed patients with AML enrolled in the Beat AML Master Trial (BAMT) at 2 academic institutions. We analyzed the diagnostic samples from patients with AML for the detection of pathogenic myeloid mutations in 8 genes (DNMT3A, FLT3, IDH1, IDH2, NPM1, TET2, TP53, and WT1) locally using the Hematologic Neoplasm Mutation Panel (50-gene myeloid indication filter) (site 1) or the GeneTrails Comprehensive Heme Panel (site 2) at the 2 institutions and compared them with the central results from the diagnostic laboratory for the BAMT, Foundation Medicine, Inc. The overall percent agreement was over 95% each in all 8 genes, with almost perfect agreement (κ > 0.906) in all but WT1, which had substantial agreement (κ = 0.848) when controlling for site. The minimal discrepancies were due to reporting variants of unknown significance (VUS) for the WT1 and TP53 genes. These results indicate that the various NGS methods used to analyze samples from patients with AML enrolled in the BAMT show high concordance, a reassuring finding given the wide use of NGS for therapeutic decision-making in AML.