Cecilia C S Yeung, Srikrishna K Narava, Ting-Chia Chang, Maria Saeed, Lauri Aicher, Lan W Beppu, Marvin S Majano, Erin M Taylor, Corinne E Camalier, Pooja Sandhuria, Olga Sala-Torra, Jessica Li, Laura M Yee, Lisa M McShane, Chris Karlovich, Richard F Little, Lyndsay Harris, James H Doroshow, Paul M Williams, Jerald P Radich, Shahanawaz Jiwani
{"title":"NCI-myeloMATCH测定的分析性能-一种髓系疾病的快速周转基因组分析测定。","authors":"Cecilia C S Yeung, Srikrishna K Narava, Ting-Chia Chang, Maria Saeed, Lauri Aicher, Lan W Beppu, Marvin S Majano, Erin M Taylor, Corinne E Camalier, Pooja Sandhuria, Olga Sala-Torra, Jessica Li, Laura M Yee, Lisa M McShane, Chris Karlovich, Richard F Little, Lyndsay Harris, James H Doroshow, Paul M Williams, Jerald P Radich, Shahanawaz Jiwani","doi":"10.1016/j.jmoldx.2025.05.001","DOIUrl":null,"url":null,"abstract":"<p><p>myeloMATCH is a National Cancer Institute precision medicine clinical trial initiative to evaluate treatments for acute myeloid leukemia and myelodysplastic syndrome based on a patient's diagnostic presenting clinical and genetic profile. The National Cancer Institute myeloid assay version 2 (NMAv2) uses the Ion Torrent Genexus System, an automated platform with <48-hour turnaround from specimen receipt to reporting, to provide regulatory-compliant use for myeloMATCH across two independent clinical laboratories with harmonized workflows. Using marrow aspirate or peripheral blood clinical specimens, cell lines, and contrived reference materials, NMAv2 exhibited 99% sensitivity for 291 known mutations and 100% specificity. High reproducibility detecting all reportable variants was observed, with >98% mean positive percentage agreement and 100% negative percent agreement across six reproducibility assessments. Reproducibility experiments of companion diagnostic biomarkers (1 to 1.5× clinical limit of reporting) showed 100% positive percentage agreement and negative percent agreement. The limit of detection was 0.06% for hotspot single-nucleotide variants, 0.16% for non-hotspot single-nucleotide variants, 0.51% for hotspot insertion/deletions, approximately 1% for non-hotspot insertion/deletions, 0.23% for FLT3-internal tandem duplications, and ≤40 reads at 0.1% tumor content for fusions. Concordance of 99.39% was observed in orthogonal assays testing 76 blinded myeloid specimens in the sensitivity study, and 100% concordance was observed in testing 54 FLT3-internal tandem duplication specimens. The results show that NMAv2 has high specificity, sensitivity, accuracy, and reproducibility, and it can rapidly characterize genomic alterations in acute myeloid leukemia and myelodysplastic syndrome.</p>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":" ","pages":""},"PeriodicalIF":3.4000,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Analytical Performance of the NCI-myeloMATCH Assay: A Rapid Turnaround Genomic Profiling Assay for Myeloid Disorders.\",\"authors\":\"Cecilia C S Yeung, Srikrishna K Narava, Ting-Chia Chang, Maria Saeed, Lauri Aicher, Lan W Beppu, Marvin S Majano, Erin M Taylor, Corinne E Camalier, Pooja Sandhuria, Olga Sala-Torra, Jessica Li, Laura M Yee, Lisa M McShane, Chris Karlovich, Richard F Little, Lyndsay Harris, James H Doroshow, Paul M Williams, Jerald P Radich, Shahanawaz Jiwani\",\"doi\":\"10.1016/j.jmoldx.2025.05.001\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>myeloMATCH is a National Cancer Institute precision medicine clinical trial initiative to evaluate treatments for acute myeloid leukemia and myelodysplastic syndrome based on a patient's diagnostic presenting clinical and genetic profile. The National Cancer Institute myeloid assay version 2 (NMAv2) uses the Ion Torrent Genexus System, an automated platform with <48-hour turnaround from specimen receipt to reporting, to provide regulatory-compliant use for myeloMATCH across two independent clinical laboratories with harmonized workflows. Using marrow aspirate or peripheral blood clinical specimens, cell lines, and contrived reference materials, NMAv2 exhibited 99% sensitivity for 291 known mutations and 100% specificity. High reproducibility detecting all reportable variants was observed, with >98% mean positive percentage agreement and 100% negative percent agreement across six reproducibility assessments. Reproducibility experiments of companion diagnostic biomarkers (1 to 1.5× clinical limit of reporting) showed 100% positive percentage agreement and negative percent agreement. The limit of detection was 0.06% for hotspot single-nucleotide variants, 0.16% for non-hotspot single-nucleotide variants, 0.51% for hotspot insertion/deletions, approximately 1% for non-hotspot insertion/deletions, 0.23% for FLT3-internal tandem duplications, and ≤40 reads at 0.1% tumor content for fusions. Concordance of 99.39% was observed in orthogonal assays testing 76 blinded myeloid specimens in the sensitivity study, and 100% concordance was observed in testing 54 FLT3-internal tandem duplication specimens. The results show that NMAv2 has high specificity, sensitivity, accuracy, and reproducibility, and it can rapidly characterize genomic alterations in acute myeloid leukemia and myelodysplastic syndrome.</p>\",\"PeriodicalId\":50128,\"journal\":{\"name\":\"Journal of Molecular Diagnostics\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.4000,\"publicationDate\":\"2025-05-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Molecular Diagnostics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.jmoldx.2025.05.001\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PATHOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Molecular Diagnostics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.jmoldx.2025.05.001","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PATHOLOGY","Score":null,"Total":0}
Analytical Performance of the NCI-myeloMATCH Assay: A Rapid Turnaround Genomic Profiling Assay for Myeloid Disorders.
myeloMATCH is a National Cancer Institute precision medicine clinical trial initiative to evaluate treatments for acute myeloid leukemia and myelodysplastic syndrome based on a patient's diagnostic presenting clinical and genetic profile. The National Cancer Institute myeloid assay version 2 (NMAv2) uses the Ion Torrent Genexus System, an automated platform with <48-hour turnaround from specimen receipt to reporting, to provide regulatory-compliant use for myeloMATCH across two independent clinical laboratories with harmonized workflows. Using marrow aspirate or peripheral blood clinical specimens, cell lines, and contrived reference materials, NMAv2 exhibited 99% sensitivity for 291 known mutations and 100% specificity. High reproducibility detecting all reportable variants was observed, with >98% mean positive percentage agreement and 100% negative percent agreement across six reproducibility assessments. Reproducibility experiments of companion diagnostic biomarkers (1 to 1.5× clinical limit of reporting) showed 100% positive percentage agreement and negative percent agreement. The limit of detection was 0.06% for hotspot single-nucleotide variants, 0.16% for non-hotspot single-nucleotide variants, 0.51% for hotspot insertion/deletions, approximately 1% for non-hotspot insertion/deletions, 0.23% for FLT3-internal tandem duplications, and ≤40 reads at 0.1% tumor content for fusions. Concordance of 99.39% was observed in orthogonal assays testing 76 blinded myeloid specimens in the sensitivity study, and 100% concordance was observed in testing 54 FLT3-internal tandem duplication specimens. The results show that NMAv2 has high specificity, sensitivity, accuracy, and reproducibility, and it can rapidly characterize genomic alterations in acute myeloid leukemia and myelodysplastic syndrome.
期刊介绍:
The Journal of Molecular Diagnostics, the official publication of the Association for Molecular Pathology (AMP), co-owned by the American Society for Investigative Pathology (ASIP), seeks to publish high quality original papers on scientific advances in the translation and validation of molecular discoveries in medicine into the clinical diagnostic setting, and the description and application of technological advances in the field of molecular diagnostic medicine. The editors welcome for review articles that contain: novel discoveries or clinicopathologic correlations including studies in oncology, infectious diseases, inherited diseases, predisposition to disease, clinical informatics, or the description of polymorphisms linked to disease states or normal variations; the application of diagnostic methodologies in clinical trials; or the development of new or improved molecular methods which may be applied to diagnosis or monitoring of disease or disease predisposition.