TY - JOUR AU - Fanny Drieux, AU - Philippe Ruminy, AU - Ahmad Abdel-Sater, AU - François Lemonnier, AU - Pierre-Julien Viailly, AU - Virginie Fataccioli, AU - Vinciane Marchand, AU - Bettina Bisig, AU - Audrey Letourneau, AU - Marie Parrens, AU - Céline Bossard, AU - Julie Bruneau, AU - Pamela Dobay, AU - Liana Veresezan, AU - Aurélie Dupuy, AU - Anaïs Pujals, AU - Cyrielle Robe, AU - Nouhoum Sako, AU - Christiane Copie-Bergman, AU - Marie-Hélène Delfau-Larue, AU - Jean-Michel Picquenot, AU - Hervé Tilly, AU - Richard Delarue, AU - Fabrice Jardin, AU - Laurence de Leval, AU - Philippe Gaulard, PY - 2020/06/01 Y2 - 2024/03/28 TI - Defining signatures of peripheral T-cell lymphoma with a targeted 20-marker gene expression profiling assay JF - Haematologica JA - haematol VL - 105 IS - 6 SE - Articles DO - 10.3324/haematol.2019.226647 UR - https://haematologica.org/article/view/9434 SP - 1582-1592 AB - 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. ER -