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

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

  • Drieux F INSERM U1245, Centre Henri Becquerel, Rouen, France.
  • Ruminy P INSERM U1245, Centre Henri Becquerel, Rouen, France philippe.ruminy@chb.unicancer.fr.
  • Abdel-Sater A INSERM U1245, Centre Henri Becquerel, Rouen, France.
  • Lemonnier F INSERM U955 and Université Paris-Est, Créteil, France.
  • Viailly PJ INSERM U1245, Centre Henri Becquerel, Rouen, France.
  • Fataccioli V INSERM U955 and Université Paris-Est, Créteil, France.
  • Marchand V INSERM U1245, Centre Henri Becquerel, Rouen, France.
  • Bisig B Institut de Pathologie, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
  • Letourneau A Institut de Pathologie, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
  • Parrens M Service d'Anatomie et Cytologie Pathologiques, Hôpital Haut-Lévêque, CHU de Bordeaux, France.
  • Bossard C Service d'Anatomie et Cytologie Pathologiques, CHU de Nantes, France.
  • Bruneau J Service d'Anatomie et Cytologie Pathologiques, Hôpital Universitaire Necker - Enfants Malades, Assistance Publique - Hôpitaux de Paris (APHP), Paris, France.
  • Dobay P Institut de Pathologie, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
  • Veresezan L INSERM U1245, Centre Henri Becquerel, Rouen, France.
  • Dupuy A INSERM U955 and Université Paris-Est, Créteil, France.
  • Pujals A INSERM U955 and Université Paris-Est, Créteil, France.
  • Robe C INSERM U955 and Université Paris-Est, Créteil, France.
  • Sako N INSERM U955 and Université Paris-Est, Créteil, France.
  • Copie-Bergman C INSERM U955 and Université Paris-Est, Créteil, France.
  • Delfau-Larue MH INSERM U955 and Université Paris-Est, Créteil, France.
  • Picquenot JM INSERM U1245, Centre Henri Becquerel, Rouen, France.
  • Tilly H INSERM U1245, Centre Henri Becquerel, Rouen, France.
  • Delarue R Service Hématologie Adultes, Hôpital Universitaire Necker - Enfants Malades, Assistance Publique - Hôpitaux de Paris (APHP), Paris, France.
  • Jardin F INSERM U1245, Centre Henri Becquerel, Rouen, France.
  • de Leval L Institut de Pathologie, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
  • Gaulard P INSERM U955 and Université Paris-Est, Créteil, France philippe.gaulard@aphp.fr.
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  • 2019-09-07
Published in:
  • Haematologica. - 2020
Hematology
English 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 TFH-derived lymphomas divided into two subgroups according to a predominant TFH (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 TFH, 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.
Language
  • English
Open access status
gold
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https://sonar.ch/global/documents/278246
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