Samples from patients with AML show high concordance in detection of mutations by NGS at local institutions vs central laboratories Journal Article
| Authors: | Borate, U.; Yang, F.; Press, R.; Ruppert, A. S.; Jones, D.; Caruthers, S.; Zhao, W.; Vergilio, J. A.; Pavlick, D. C.; Juckett, L.; Norris, B.; Bucy, T.; Burd, A.; Stein, E. M.; Patel, P.; Baer, M. R.; Stock, W.; Schiller, G.; Blum, W.; Kovacsovics, T.; Litzow, M.; Foran, J.; Heerema, N. A.; Rosenberg, L.; Marcus, S.; Yocum, A.; Stefanos, M.; Druker, B.; Byrd, J. C.; Levine, R. L.; Mims, A. |
| Article Title: | Samples from patients with AML show high concordance in detection of mutations by NGS at local institutions vs central laboratories |
| 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. © 2023 American Society of Hematology. All rights reserved. |
| Keywords: | controlled study; gene mutation; protein p53; laboratory test; tet2 gene; dna methyltransferase 3a; isocitrate dehydrogenase 1; cd135 antigen; nucleophosmin; idh1 gene; idh2 gene; acute myeloid leukemia; tp53 gene; high throughput sequencing; dnmt3a gene; npm1 gene; flt3 gene; isocitrate dehydrogenase 2; human; article |
| Journal Title: | Blood Advances |
| Volume: | 7 |
| Issue: | 20 |
| ISSN: | 2473-9529 |
| Publisher: | American Society of Hematology |
| Date Published: | 2023-10-24 |
| Start Page: | 6048 |
| End Page: | 6054 |
| Language: | English |
| DOI: | 10.1182/bloodadvances.2022009008 |
| PUBMED: | 37459200 |
| PROVIDER: | scopus |
| PMCID: | PMC10582272 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work