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Defining signatures of peripheral T-cell lymphoma with a targeted 20-marker gene expression profiling assay.
- Source :
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Haematologica [Haematologica] 2020 Jun; Vol. 105 (6), pp. 1582-1592. Date of Electronic Publication: 2019 Sep 05. - Publication Year :
- 2020
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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 <subscript>FH</subscript> -derived lymphomas divided into two subgroups according to a predominant T <subscript>FH</subscript> (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 <subscript>FH</subscript> , 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.<br /> (Copyright© 2020 Ferrata Storti Foundation.)
Details
- Language :
- English
- ISSN :
- 1592-8721
- Volume :
- 105
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Haematologica
- Publication Type :
- Academic Journal
- Accession number :
- 31488561
- Full Text :
- https://doi.org/10.3324/haematol.2019.226647