Format

Send to

Choose Destination
J Mol Diagn. 2017 Nov;19(6):892-904. doi: 10.1016/j.jmoldx.2017.07.007. Epub 2017 Oct 17.

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

Author information

1
INSERM U1245, UNIROUEN, University of Normandie, Rouen, France; Department of Biological Hematology, Rouen University Hospital, Rouen, France.
2
INSERM U1245, UNIROUEN, University of Normandie, Rouen, France. Electronic address: philippe.ruminy@chb.unicancer.fr.
3
INSERM U1245, UNIROUEN, University of Normandie, Rouen, France.
4
INSERM U1245, UNIROUEN, University of Normandie, Rouen, France; LITIS EA 4108, UNIROUEN, University of Normandie, Rouen, France.
5
Department of Pathology, Centre Henri Becquerel, Rouen, France.
6
INSERM U1245, UNIROUEN, University of Normandie, Rouen, France; Department of Pathology, Centre Henri Becquerel, Rouen, France.
7
LITIS EA 4108, UNIROUEN, University of Normandie, Rouen, France.
8
INSERM UMRS872, AP-HP Necker Hospital, Paris, France.
9
INSERM U955 Team 09, AP-HP Henri Mondor Hospital, Creteil, France.
10
Functional Genomics Platform, Center for Biology and Pathology, University of Lille, Lille Cedex, France.
11
Department of Pathology, Necker Hospital, AP-HP, Université Paris Descartes Sorbonne Cité, Paris, France.
12
Department of Hematology, University Claude Bernard Lyon 1, Hospices Civils de Lyon, Pierre-Benite, France.
13
Lymphoid Malignancies Unit, Hospital Henri Mondor, Creteil, France.

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.

PMID:
29054399
DOI:
10.1016/j.jmoldx.2017.07.007
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center