Determination of Molecular Subtypes of Diffuse Large B-Cell Lymphoma Using a Reverse Transcriptase Multiplex Ligation-Dependent Probe Amplification Classifier: A CALYM Study.

Abstract

Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma. It includes three major subtypes termed germinal center B-cell-like, activated B-cell-like, and primary mediastinal B-cell lymphoma. With the emergence of novel targeted therapies, accurate methods capable of interrogating this cell-of-origin classification should soon become essential in the clinics. To address this issue, we developed a novel gene expression profiling DLBCL classifier based on reverse transcriptase multiplex ligation-dependent probe amplification. This assay simultaneously evaluates the expression of 21 markers, to differentiate primary mediastinal B-cell lymphoma, activated B-cell-like, germinal center B-cell-like, and also Epstein-Barr virus-positive DLBCLs. It was trained using 70 paraffin-embedded biopsies and validated using >160 independent samples. Compared with a reference classification established from Affymetrix U133 + 2 data, reverse transcriptase multiplex ligation-dependent probe amplification classified 85.0% samples into the expected subtype, comparing favorably with current diagnostic methods. This assay also proved to be highly efficient in detecting the MYD88 L265P mutation, even in archival paraffin-embedded tissues. This reliable, rapid, and cost-effective method uses common instruments and reagents and could thus easily be implemented into routine diagnosis workflows, to improve the management of these aggressive tumors.

• Authors: Victor Bobée, Philippe Ruminy, Vinciane Marchand, Pierre-Julien Viailly, Ahmad Abdel Sater, Liana Veresezan, Fanny Drieux, Caroline Bérard, Elodie Bohers, Sylvain Mareschal, Sydney Dubois, Jean-Philippe Jais, Karen Leroy, Martin Figeac, Jean-Michel Picquenot, Thierry Jo Molina, Gilles Salles, Corinne Haioun, Hervé Tilly, Fabrice Jardin
• Journal: The Journal of molecular diagnostics : JMD (J Mol Diagn) Vol. 19 Issue 6 Pg. 892-904 (11 2017) ISSN: 1943-7811 [Electronic] United States
• PMID: 29054399 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Chemical References

• Biomarkers, Tumor

Topics

• Biomarkers, Tumor (genetics)
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic (genetics)
• Humans
• Lymphoma, Large B-Cell, Diffuse (classification, diagnosis, genetics, pathology)
• Multiplex Polymerase Chain Reaction (methods)
• Mutation
• Oligonucleotide Array Sequence Analysis (methods)
• Paraffin Embedding
• Reverse Transcriptase Polymerase Chain Reaction (methods)