Sylvain Mareschal, Ph.D.
Bioinformatics postdoc
October 13, 2017 at 18:16
Bobée et al, JMD 2017
Related entries:
J Mol Diagn. 2017 Oct 13
pii: S1525-1578(17)30245-3
doi: 10.1016/j.jmoldx.2017.07.007
[Epub ahead of print]

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

Bobée V, Ruminy P, Marchand V, Viailly PJ, Abdel Sater A, Veresezan L, Drieux F, Bérard C, Bohers E, Mareschal S, Dubois S, Jais JP, Leroy K, Figeac M, Picquenot JM, Molina TJ, Salles G, Haioun C, Tilly H, Jardin F.

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.