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A Concordance Study Among 26 NGS Laboratories Participating in the National Cancer Institute-Molecular Analysis for Therapy Choice (NCI-MATCH) Clinical Trial

  1. Author:
    Zane, Linda K [ORCID]
    Yee, Laura M [ORCID]
    Chang,Ting-Chia [ORCID]
    Sklar, Jeffrey [ORCID]
    Yang, Guangxiao [ORCID]
    Wen, Jia Di [ORCID]
    Li, Peining [ORCID]
    Harrington, Robin [ORCID]
    Sims, David J [ORCID]
    Harper, Kneshay [ORCID]
    Trent, Jeffrey M [ORCID]
    LoBello, Janine R [ORCID]
    Szelinger, Szabolcs [ORCID]
    Benson, Kasey [ORCID]
    Zeng, Jia [ORCID]
    Poorman, Kelsey [ORCID]
    Xu, Danbin [ORCID]
    Frampton, Garrett M [ORCID]
    Pavlick, Dean C [ORCID]
    Miller, Vincent A [ORCID]
    Tandon, Bevan [ORCID]
    Swat, Wojciech [ORCID]
    Weiss, Lawrence [ORCID]
    Funari, Vincent Anthony [ORCID]
    Conroy, Jeffrey M [ORCID]
    Prescott, James L [ORCID]
    Chandra, Pranil K [ORCID]
    Ma, Charles [ORCID]
    Champion, Kristen J [ORCID]
    Baschkopf, Gregory X [ORCID]
    Fesko, Yuri A [ORCID]
    Freitas, Tracey Allen K [ORCID]
    Tomlins, Scott A [ORCID]
    Hovelson, Daniel H [ORCID]
    White, Kevin [ORCID]
    Sorrells, Shelly [ORCID]
    Tell, Robert [ORCID]
    Beaubier, Nike [ORCID]
    King, David [ORCID]
    Li, Lei [ORCID]
    Kelly, Kevin [ORCID]
    Uvalic, Jasmina [ORCID]
    Meyers, Bridgette [ORCID]
    Kolhe, Ravindra [ORCID]
    Lindeman, Neal I [ORCID]
    Baltay, Michele [ORCID]
    Sholl, Lynette M [ORCID]
    Lopategui, Jean [ORCID]
    Vail, Eric [ORCID]
    Zhang, Wenjuan [ORCID]
    Telatar, Milhan [ORCID]
    Afkhami, Michelle [ORCID]
    Hsiao, Susan J [ORCID]
    Mansukhani, Mahesh M [ORCID]
    Adams, Emily [ORCID]
    Jiang, LiQun [ORCID]
    Aldape, Kenneth D [ORCID]
    Raffeld, Mark [ORCID]
    Xi, Liqiang [ORCID]
    Stehr, Henning [ORCID]
    Segal, Jeremy P [ORCID]
    Aisner, Dara L [ORCID]
    Davies, Kurtis D [ORCID]
    Brown, Noah A [ORCID]
    Livingston, Robert J [ORCID]
    Konnick, Eric Q [ORCID]
    Song, Wei [ORCID]
    Solomon, James P [ORCID]
    Walther, Zenta [ORCID]
    McShane, Lisa M [ORCID]
    Harris, Lyndsay N [ORCID]
    Chen, Alice P [ORCID]
    Tsongalis, Gregory J [ORCID]
    Hamilton, Stanley R [ORCID]
    Flaherty, Keith T [ORCID]
    O'Dwyer, Peter J [ORCID]
    Conley, Barbara A [ORCID]
    Patton, David R [ORCID]
    Iafrate, A John [ORCID]
    Williams, P Mickey [ORCID]
    Tricoli, James V [ORCID]
    Karlovich, Chris [ORCID]

  2. Author Address

    National Cancer Institute, Rockville, MD, United States., National Cancer Institute, Bethesda, United States., Frederick National Laboratory for Cancer Research, Frederick, MD, United States., Yale University, New Haven, CT, United States., Yale University, United States., Frederick National Laboratory for Cancer Research, United States., National Cancer Institute, Frederick, MD, United States., Translational Genomics Research Institute, Phoenix, AZ, United States., Exact Sciences (United States), Phoenix, AZ, United States., Translational Genomics Research Institute, Phoenix, United States., Caris Life Sciences (United States), United States., Caris Life Sciences (United States), Phoenix, Arizona, United States., CellNetix Pathology & Laboratories, Tukwila, WA, United States., Foundation Medicine Inc., Cambridge, MA, United States., Foundation Medicine, Inc, Boston, MA, United States., EQRx, Inc, Cambridge, MA, United States., GenPath, Elmwood Park, NJ, United States., NeoGenomics (United States), United States., NeoGenomics (United States), Laguna niguel, United States., Omniseq, Inc., Buffalo, NY, United States., PathGroup, Nashville, TN, United States., Quest Diagnostics (United States), United States., Quest Diagnostics (United States), Lewisville, TX, United States., Strata Oncology, Ann Arbor, MI, United States., University of Michigan-Ann Arbor, United States., National University of Singapore, Singapore, Singapore., Tempus Labs (United States), United States., Tempus Labs, Inc., United States., Robert H. Lurie Comprehensive Cancer Center of Northwestern University, United States., Jackson Laboratory, United States., Augusta University, Augusta, GA, United States., Weill Cornell Medicine, New York, NY, United States., Brigham and Women 39;s Hospital, United States., Brigham and Women 39;s Hospital, Boston, MA, United States., Cedars-Sinai Medical Center, Los Angeles, CA, United States., Cedars-Sinai Medical Center, Los Angeles, United States., City Of Hope National Medical Center, United States., City Of Hope National Medical Center, Duarte, California, United States., Columbia University Medical Center, New York, NY, United States., Columbia University, New York, NY, United States., Johns Hopkins Medical Institutions, Baltimore, MD, United States., Johns Hopkins Medical Institutions, Baltimore, United States., National Cancer Institute, Bethesda, Maryland, United States., National Cancer Institute, Bethesda, MD, United States., Stanford University, Stanford, CA, United States., University of Chicago, Chicago, IL, United States., University of Colorado Anschutz Medical Campus, United States., University of Colorado Anschutz Medical Campus, Aurora, CO, United States., University of Michigan-Ann Arbor, Ann Arbor, Michigan, United States., University of Washington, Seattle, WA, United States., University of California San Diego Medical Center, La Jolla, CA, United States., Weill Cornell Medical College, New York, NY, United States., National Institutes of Health, Bethesda, MD, United States., Dartmouth-Hitchcock Medical Center, Lebanon, NH, United States., City Of Hope National Medical Center, Irwindale, California, United States., Massachusetts General Hospital Cancer Center, Boston, MA, United States., University of Pennsylvania, Philadelphia, PA, United States., National Cancer Institute, Northport, MI, United States., Massachusetts General Hospital, Boston, MA, United States.,
    1. Year: 2025
    2. Date: Jun 04
    3. Epub Date: 2025 06 04
  2. Journal: Clinical Cancer Research : an official journal of the American Association for Cancer Research
  4. Type of Article: Article
  1. Abstract:

    NCI selected a network of CLIA-certified laboratories performing routine NGS tumor testing to identify patients for the NCI-MATCH trial. This large network provided a unique opportunity to compare variant detection and reporting between a wide range of testing platforms. Twenty-eight NGS assays from 26 laboratories within the NCI-MATCH network, including the NCI-MATCH central laboratory (CL) and 11 commercial and 14 academic designated laboratories (DL), were used for this study. DNA from 8 cell lines and 2 clinical samples were sequenced. Pairwise comparisons in variant detection and reporting between each DL and CL were performed for SNV, Indel, and CNV variant classes. We observed high concordance in variant detection between CL and DL for SNVs and Indels (Average Positive Agreement, APA>95.4% for all pairwise comparisons) but lower concordance for variant reporting after analysis pipeline filtering. We observed much higher agreement between CL and assays using amplification as the target enrichment method (84.2%< APA=95.7%, average APA=88.7%) than with other assays using hybridization capture (69.7%< APA=93.8%, average APA=77.4%) due to blacklisting of actionable variants in low complexity regions. For CNV reporting, we observed high agreement (APA>82%) except between CL and 2 assays (APA=76.9 and 71.4%) due to differences in estimation of copy numbers. Notably, for all variants, differences in variant interpretation also contributed to reporting discrepancies. This study indicates that different NGS tumor profiling tests currently in widespread clinical use achieve high concordance between assays in variant detection. For variant reporting, observed discrepancies are mainly introduced during the bioinformatics analysis.

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External Sources

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  2. DOI: 10.1158/1078-0432.CCR-24-2188
  3. PMID: 40465838
  4. PII : 762857

Library Notes

  1. Fiscal Year: FY2024-2025
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