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Lookup NU author(s): Claire Schwab, Professor Christine Harrison FRCPath FMedSci
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).
© 2017 American Society for Investigative Pathology and the Association for Molecular Pathology Recurrent and clonal genetic alterations are characteristic of different subtypes of T- and B-cell lymphoblastic leukemia (ALL), and several subtypes are strong independent predictors of clinical outcome. A next-generation sequencing–based multiplex ligation-dependent probe amplification variant (digitalMLPA) has been developed enabling simultaneous detection of copy number alterations (CNAs) of up to 1000 target sequences. This novel digitalMLPA assay was designed and optimized to detect CNAs of 56 key target genes and regions in ALL. A set of digital karyotyping probes has been included for the detection of gross ploidy changes, to determine the extent of CNAs, while also serving as reference probes for data normalization. Sixty-seven ALL patient samples (including B- and T-cell ALL), previously characterized for genetic aberrations by standard MLPA, array comparative genomic hybridization, and/or single-nucleotide polymorphism array, were analyzed single blinded using digitalMLPA. The digitalMLPA assay reliably identified whole chromosome losses and gains (including high hyperdiploidy), whole gene deletions or gains, intrachromosomal amplification of chromosome 21, fusion genes, and intragenic deletions, which were confirmed by other methods. Furthermore, subclonal alterations were reliably detected if present in at least 20% to 30% of neoplastic cells. The diagnostic sensitivity of the digitalMLPA assay was 98.9%, and the specificity was 97.8%. These results merit further consideration of digitalMLPA as a valuable alternative for genetic work-up of newly diagnosed ALL patients.
Author(s): Benard-Slagter A, Zondervan I, de Groot K, Ghazavi F, Sarhadi V, Van Vlierberghe P, De Moerloose B, Schwab C, Vettenranta K, Harrison CJ, Knuutila S, Schouten J, Lammens T, Savola S
Publication type: Article
Publication status: Published
Journal: Journal of Molecular Diagnostics
Year: 2017
Volume: 19
Issue: 5
Pages: 659-672
Print publication date: 01/09/2017
Online publication date: 19/07/2017
Acceptance date: 03/05/2017
Date deposited: 18/10/2017
ISSN (print): 1525-1578
ISSN (electronic): 1943-7811
Publisher: Elsevier B.V.
URL: https://doi.org/10.1016/j.jmoldx.2017.05.004
DOI: 10.1016/j.jmoldx.2017.05.004
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