Sylvain Mareschal, Ph.D.
Bioinformatics engineer
April 16, 2015 at 18:05
Mareschal, Ruminy et al, JMD 2015
Related entries:
The Journal of Molecular Diagnotics. 2015 May;17(3):209-334
doi: 10.1016/j.jmoldx.2015.01.007

Accurate Classification of Germinal Center B-Cell–Like/Activated B-Cell–Like Diffuse Large B-Cell Lymphoma Using a Simple and Rapid Reverse Transcriptase–Multiplex Ligation-Dependent Probe Amplification Assay - A CALYM Study

Mareschal S and Ruminy P, Bagacean C, Marchand V, Cornic M, Jaïs JP, Figeac M, Picquenot JM, Molina TJ, Fest T, Salles G, Haioun C, Leroy K, Tilly K, Jardin F.

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.
Pubmed, PMID: 25891505

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