Mutations in the gene encoding nucleophosmin (NPM1) carry a prognostic value for patients with acute myeloid leukemia (AML). Various techniques are currently being used to detect these mutations in routine molecular diagnostics. Incorporation of accurate NPM1 mutation detection on a gene expression platform would enable simultaneous detection with various other expression biomarkers. Here we present an array-based mutation detection using custom probes for NPM1 WT mRNA and NPM1 type A, B, and D mutant mRNA. This method was 100% accurate on a training cohort of 505 newly diagnosed unselected AML cases. Validation on an independent cohort of 143 normal-karyotype AML cases revealed no false-negative results, and one false positive (sensitivity 100.0% and specificity 98.7%). Based on this, we conclude that this method provides a reliable method for NPM1 mutation detection. The method can be applied to other genes/mutations as long as the mutant alleles are sufficiently highly expressed.

RNA probe, acute granulocytic leukemia, article, false negative result, gene expression, gene mutation, human, karyotype, major clinical study, sensitivity and specificity,
Genetic Testing and Molecular Biomarkers
Erasmus MC: University Medical Center Rotterdam

van Vliet, M.H, Dumee, B, Simons, E, Bullinger, L, Döhner, K, Viëtor, H, … van Beers, E.H. (2013). Detection of mutant NPM1 mRNA in acute myeloid leukemia using custom gene expression arrays. Genetic Testing and Molecular Biomarkers, 17(4), 295–300. doi:10.1089/gtmb.2012.0344