Defining signatures of peripheral T-cell lymphoma with a targeted 20-marker gene expression profiling assay.

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Serval ID
serval:BIB_99596E330272
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Defining signatures of peripheral T-cell lymphoma with a targeted 20-marker gene expression profiling assay.
Journal
Haematologica
Author(s)
Drieux F., Ruminy P., Abdel-Sater A., Lemonnier F., Viailly P.J., Fataccioli V., Marchand V., Bisig B., Letourneau A., Parrens M., Bossard C., Bruneau J., Dobay P., Veresezan L., Dupuy A., Pujals A., Robe C., Sako N., Copie-Bergman C., Delfau-Larue M.H., Picquenot J.M., Tilly H., Delarue R., Jardin F., de Leval L., Gaulard P.
Contributor(s)
Gaulard P.
ISSN
1592-8721 (Electronic)
ISSN-L
0390-6078
Publication state
Published
Issued date
06/2020
Peer-reviewed
Oui
Volume
105
Number
6
Pages
1582-1592
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Peripheral T-cell lymphoma comprises a heterogeneous group of mature non-Hodgkin lymphomas. Their diagnosis is challenging, with up to 30% of cases remaining unclassifiable and referred to as "not otherwise specified". We developed a reverse transcriptase-multiplex ligation-dependent probe amplification gene expression profiling assay to differentiate the main T-cell lymphoma entities and to study the heterogeneity of the "not specified" category. The test evaluates the expression of 20 genes, including 17 markers relevant to T-cell immunology and lymphoma biopathology, one Epstein-Barr virus-related transcript, and variants of RHOA (G17V) and IDH2 (R172K/T). By unsupervised hierarchical clustering, our assay accurately identified 21 of 21 ALK-positive anaplastic large cell lymphomas, 16 of 16 extranodal natural killer (NK)/T-cell lymphomas, 6 of 6 hepatosplenic T-cell lymphomas, and 13 of 13 adult T-cell leukemia/lymphomas. ALK-negative anaplastic lymphomas (n=34) segregated into one cytotoxic cluster (n=10) and one non-cytotoxic cluster expressing Th2 markers (n=24) and enriched in DUSP22-rearranged cases. The 63 T <sub>FH</sub> -derived lymphomas divided into two subgroups according to a predominant T <sub>FH</sub> (n=50) or an enrichment in Th2 (n=13) signatures. We next developed a support vector machine predictor which attributed a molecular class to 27 of 77 not specified T-cell lymphomas: 17 T <sub>FH</sub> , five cytotoxic ALK-negative anaplastic and five NK/T-cell lymphomas. Among the remaining cases, we identified two cell-of-origin subgroups corresponding to cytotoxic/Th1 (n=19) and Th2 (n=24) signatures. A reproducibility test on 40 cases yielded a 90% concordance between three independent laboratories. This study demonstrates the applicability of a simple gene expression assay for the classification of peripheral T-cell lymphomas. Its applicability to routinely-fixed samples makes it an attractive adjunct in diagnostic practice.
Keywords
Aggressive Non-Hodgkin's Lymphoma, Cytogenetics and Molecular Genetics, Immunophenotyping, Peripheral T-cell lymphoma, RT-MLPA
Pubmed
Web of science
Open Access
Yes
Create date
13/09/2019 11:16
Last modification date
30/07/2020 5:21
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