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

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Bobée, Victor | Ruminy, Philippe | Marchand, Vinciane | Viailly, Pierre-Julien | Abdel Sater, Ahmad | Veresezan, Liana | Drieux, Fanny | Berard, Caroline, C. | Bohers, Elodie | Mareschal, Sylvain | Dubois, Sydney | Jais, Jean-Philippe | Leroy, Karen | Figeac, Martin | Picquenot, Jean-Michel | Molina, Thierry Jo | Salles, Gilles | Haioun, Corinne | Tilly, Hervé | Jardin, Fabrice

Edité par CCSD ; American Society for Investigative Pathology (ASIP) -

International audience. 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.

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