Hybridization capture-based next-generation sequencing reliably detects FLT3 mutations and classifies FLT3-internal tandem duplication allelic ratio in acute myeloid leukemia: A comparative study to standard fragment analysis
Modern Pathology Sep 09, 2019
He R, Devine DJ, Tu ZJ, et al. - Through a comparative study with fragment analysis, researchers retrospectively analyzed their experience using a custom-designed, hybridization capture-based, targeted next-generation sequencing panel in order to discover FLT3 mutations and classify FLT3-internal tandem duplication allelic ratio in acute myeloid leukemia among 7,902 cases. A total of 128 of 136 dual-tested, positive cases, showed concordant high/low allelic ratio classifications. The remaining 6% explicated the borderline low allelic ratio by next-generation sequencing. In FLT3-tyrosine kinase domain mutation detection, the two methods were concordant at the hotspot D835/I836 targeted by fragment analysis. Moreover, in regions not covered by fragment analysis, seven mutations that may profit from FLT3 inhibitor therapy were discovered by next-generation sequencing. In conclusion, using a hybridization capture-based chemistry and optimized bioinformatics pipeline, it was revealed that next-generation sequencing can assuredly identify FLT3-internal tandem duplication and for acute myeloid leukemia risk stratification, classify its allelic ratio. Further, in FLT3 mutation detection next-generation sequencing also reveals superior comprehensiveness and may further enhance personalized, targeted therapy in acute myeloid leukemia.
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