Back to Search
Start Over
A New Next-Generation Sequencing Strategy for the Simultaneous Analysis of Mutations and Chromosomal Rearrangements at DNA Level in Acute Myeloid Leukemia Patients.
- Source :
-
The Journal of molecular diagnostics : JMD [J Mol Diagn] 2020 Jan; Vol. 22 (1), pp. 60-71. Date of Electronic Publication: 2019 Oct 09. - Publication Year :
- 2020
-
Abstract
- Acute myeloid leukemias (AMLs) are currently genomically characterized by karyotype, fluorescence in situ hybridization (FISH), real-time quantitative PCR, and DNA sequencing. Next-generation sequencing offers the promise of detecting all genomic lesions in a single run. However, technical limitations have hampered the detection of chromosomal rearrangements, so most studies are limited to somatic mutation assessment or require the use of RNA-based strategies. To overcome these limitations, we designed a targeted-DNA capture next-generation sequencing approach associated with easy-to-perform public bioinformatic tools for one-step identification of translocations, inversions, and somatic mutations in AML. Thirty well-characterized newly diagnosed myeloid leukemia patients (27 AML and 3 chronic myeloid leukemia) were tested with the panel. Twenty-three of 24 known rearrangements, as well as one novel fusion gene that could not be detected by karyotype/fluorescence in situ hybridization/real-time quantitative PCR, were detected. This strategy also identified all chromosomal breakpoints as potential targets for future high-sensitive minimal residual disease studies. In addition, mutation analysis revealed the presence of missense protein-coding alterations in at least 1 of the 32 genes evaluated in 21 of 30 patients (70%). This strategy may represent a time- and cost-effective diagnostic method for molecular characterization in AML.<br /> (Copyright © 2020 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Base Sequence
Bone Marrow
Chromosome Breakpoints
DNA Mutational Analysis methods
Data Accuracy
Humans
In Situ Hybridization, Fluorescence methods
Karyotyping methods
Real-Time Polymerase Chain Reaction methods
Sensitivity and Specificity
Sequence Analysis, DNA methods
Chromosome Aberrations
DNA genetics
High-Throughput Nucleotide Sequencing methods
Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics
Leukemia, Myeloid, Acute genetics
Mutation, Missense
Subjects
Details
- Language :
- English
- ISSN :
- 1943-7811
- Volume :
- 22
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- The Journal of molecular diagnostics : JMD
- Publication Type :
- Academic Journal
- Accession number :
- 31605801
- Full Text :
- https://doi.org/10.1016/j.jmoldx.2019.08.002