J Mol Diagn. 2018 Dec 18. pii: S1525-1578(17)30614-1. doi: 10.1016/j.jmoldx.2018.09.009. [Epub ahead of print]
Clinical Utility Of A Next-Generation Sequencing Panel For Acute Myeloid Leukemia Diagnostics.
Alonso CM1, Llop M2, Sargas C3, Pedrola L4, Panadero J4, Hervás D5, Cervera J6, Such E6, Ibáñez M6, Ayala R7, Martínez-López J8, Onecha E9, de Juan I10, Palanca S10, Martínez-Cuadrón D3, Rodríguez-Veiga R3, Boluda B3, Montesinos P6, Sanz G6, Sanz MA6, Barragán E11.
Abstract
Next-generation-sequencing (NGS) has redefined the genetic landscape of acute myeloid leukemia (AML) providing new molecular markers for diagnostic and prognostic classifications. However, its application in the clinical setting is still challenging. We hypothesized that a 19-gene AML-targeted NGS panel could be a valid approach to obtain clinically relevant information. Thus, we assessed the ability of this panel to classify AML patients according to diagnostic and prognostic indexes in a cohort of 162 patients. The assay yielded a median read depth above 2000X, with 88% of on-target reads and a mean uniformity above 93% without significant global strand bias. The method was sensitive and specific, with a valid performance at the clinical variant allele frequency cut-off of 3% for point mutations and 5% for INDELs. Three-hundred and thirty-nine variants were found (36% INDELs and 64% SNVs). Concordance between NGS and other conventional techniques was 100%, but the NGS approach was able to identify more clinically relevant mutations. Finally, all patients could be classified into one of the 2016 WHO diagnostic categories and virtually all into the recently proposed prognostic indexes (2017 ELN and Genomic classification). To sum up, we validate a reliable and reproducible method for AML diagnosis and demonstrate that small, well-designed NGS panels are sufficient to guide clinical decisions according to the current standards.
- PMID:
- 30576870
- DOI:
- 10.1016/j.jmoldx.2018.09.009
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