Clinical Validation and Implementation of a Measurable Residual Disease Assay for NPM1 in Acute Myeloid Leukemia by Error-Corrected Next-Generation Sequencing.
Journal
Molecular diagnosis & therapy
ISSN: 1179-2000
Titre abrégé: Mol Diagn Ther
Pays: New Zealand
ID NLM: 101264260
Informations de publication
Date de publication:
12 2019
12 2019
Historique:
pubmed:
2
11
2019
medline:
13
5
2020
entrez:
2
11
2019
Statut:
ppublish
Résumé
Nucleophosmin 1 (NPM1) is one of the most commonly mutated genes in acute myeloid leukemia, with mutations observed in approximately 30% of all adult cases. The persistence of NPM1 mutations following chemotherapy is associated with a greater risk of relapse as well as a lower rate of survival, making NPM1 measurable residual disease (MRD) an informative clinical target. Herein, we have developed a straightforward unique molecular identifier (UMI)-based amplicon next-generation sequencing method for the detection of NPM1-mutated MRD that addresses some of the limitations present in other assays. The NPM1 assay allowed for accurate counting of individual mutant and wild-type molecules down to 0.01% variant allelic frequency. In silico contamination experiments highlighted the ability of this UMI methodology to maximize specificity through dramatic reductions in sequencing/demultiplexing bleed-through error. Performance and clinical utility of the NPM1 MRD assay are established via both validation experiments and analyses of live performance over 1.5 years of routine clinical service.
Sections du résumé
BACKGROUND
Nucleophosmin 1 (NPM1) is one of the most commonly mutated genes in acute myeloid leukemia, with mutations observed in approximately 30% of all adult cases. The persistence of NPM1 mutations following chemotherapy is associated with a greater risk of relapse as well as a lower rate of survival, making NPM1 measurable residual disease (MRD) an informative clinical target.
METHODS
Herein, we have developed a straightforward unique molecular identifier (UMI)-based amplicon next-generation sequencing method for the detection of NPM1-mutated MRD that addresses some of the limitations present in other assays.
RESULTS
The NPM1 assay allowed for accurate counting of individual mutant and wild-type molecules down to 0.01% variant allelic frequency. In silico contamination experiments highlighted the ability of this UMI methodology to maximize specificity through dramatic reductions in sequencing/demultiplexing bleed-through error.
CONCLUSION
Performance and clinical utility of the NPM1 MRD assay are established via both validation experiments and analyses of live performance over 1.5 years of routine clinical service.
Identifiants
pubmed: 31673932
doi: 10.1007/s40291-019-00436-8
pii: 10.1007/s40291-019-00436-8
doi:
Substances chimiques
Biomarkers, Tumor
0
NPM1 protein, human
0
Nuclear Proteins
0
Nucleophosmin
117896-08-9
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
791-802Références
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