Abstract |
Diffuse large B-cell lymphoma, the most common non-Hodgkin lymphoma, is subdivided into germinal center B-cell-like and activated B-cell-like subtypes. Unfortunately, these lymphomas are difficult to differentiate in routine diagnosis, impeding the development of treatments. Patients with these lymphomas can benefit from specific therapies. We therefore developed a simple and rapid classifier based on a reverse transcriptase multiplex ligation-dependent probe amplification assay and 14 gene signatures. Compared with the Affymetrix U133+2 gold standard, all 46 samples (95% CI, 92%-100%) of a validation cohort classified by both techniques were attributed to the expected subtype. Similarly, 93% of the 55 samples (95% CI, 82%-98%) of a second independent series characterized with a mid-throughput gene expression profiling method were classified correctly. Unclassifiable sample proportions reached 13.2% and 13.8% in these cohorts, comparable with the frequency originally reported. The developed assay was also sensitive enough to obtain reliable results from formalin-fixed, paraffin-embedded samples and flexible enough to include prognostic factors such as MYC/BCL2 co-expression. Finally, in a series of 135 patients, both overall (P = 0.01) and progression-free (P = 0.004) survival differences between the two subtypes were confirmed. Because the multiplex ligation-dependent probe amplification method is already in use and requires only common instruments and reagents, it could easily be applied to clinical trial patient stratification to help in treatment decisions.
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Authors | Sylvain Mareschal, Philippe Ruminy, Cristina Bagacean, Vinciane Marchand, Marie Cornic, Jean-Philippe Jais, Martin Figeac, Jean-Michel Picquenot, Thierry Jo Molina, Thierry Fest, Gilles Salles, Corinne Haioun, Karen Leroy, Hervé Tilly, Fabrice Jardin |
Journal | The Journal of molecular diagnostics : JMD
(J Mol Diagn)
(Apr 09 2015)
ISSN: 1943-7811 [Electronic] United States |
PMID | 25891505
(Publication Type: Journal Article)
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Copyright | Copyright © 2015 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved. |