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Next-generation sequencing and real-time quantitative PCR for minimal residual disease detection in B-cell disorders.

Abstract：

:In this study, we compared immunoglobulin heavy-chain-gene-based minimal residual disease (MRD) detection by real-time quantitative PCR (RQ-PCR) and next-generation sequencing (NGS) to assess whether NGS could overcome some limitations of RQ-PCR and further increase sensitivity, specificity, accuracy and reproducibility. In total, 378 samples from 55 patients with acute lymphoblastic leukemia (ALL), mantle cell lymphoma (MCL) or multiple myeloma (MM) were investigated for clonotype identification, clonotype identity and comparability of MRD results. Forty-five clonotypes were identified by RQ-PCR and 49 by NGS. Clonotypes identified by both tools were identical or >97% homologous in 96% of cases. Both tools were able to routinely reach a sensitivity level of 1 × E-05. A good correlation of MRD results was observed (R=0.791, P<0.001), with excellent concordance in 79.6% of cases. Few discordant cases were observed across all disease subtypes. NGS showed at least the same level of sensitivity as allele-specific oligonucleotides-PCR, without the need for patient-specific reagents. We conclude that NGS is an effective tool for MRD monitoring in ALL, MCL and MM. Prospective comparative analysis of unselected cases is required to validate the clinical impact of NGS-based MRD assessment.

journal_name

Leukemia

journal_title

Leukemia

authors

Ladetto M,Brüggemann M,Monitillo L,Ferrero S,Pepin F,Drandi D,Barbero D,Palumbo A,Passera R,Boccadoro M,Ritgen M,Gökbuget N,Zheng J,Carlton V,Trautmann H,Faham M,Pott C

doi

10.1038/leu.2013.375

subject

Has Abstract

pub_date

2014-06-01 00:00:00

pages

1299-307

issue

6

eissn

0887-6924

issn

1476-5551

pii

leu2013375

journal_volume

28

pub_type

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