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Gene expression profiling identifies molecular subgroups among nodal peripheral T-cell lymphomas

Abstract

The classification of peripheral T-cell lymphomas (PTCL) is still a matter of debate. To establish a molecular classification of PTCL, we analysed 59 primary nodal T-cell lymphomas using cDNA microarrays, including 56 PTCL and three T-lymphoblastic lymphoma (T-LBL). The expression profiles could discriminate angioimmunoblastic lymphoma, anaplastic large-cell lymphoma and T-LBL. In contrast, cases belonging to the broad category of ‘PTCL, unspecified’ (PTCL-U) did not share a single molecular profile. Using a multiclass predictor, we could separate PTCL-U into three molecular subgroups called U1, U2 and U3. The U1 gene expression signature included genes known to be associated with poor outcome in other tumors, such as CCND2. The U2 subgroup was associated with overexpression of genes involved in T-cell activation and apoptosis, including NFKB1 and BCL-2. The U3 subgroup was mainly defined by overexpression of genes involved in the IFN/JAK/STAT pathway. It comprised a majority of histiocyte-rich PTCL samples. Gene Ontology annotations revealed different functional profile for each subgroup. These results suggest the existence of distinct subtypes of PTCL-U with specific molecular profiles, and thus provide a basis to improve their classification and to develop new therapeutic targets.

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Acknowledgements

This work was supported by the Institut National de la Santé et de la Recherche Médicale (INSERM), by grants 3684 from the Association pour la Recherche sur le Cancer (ARC) and grants from the French Ministries of Health and Research (Canceropole project). Benoît Ballester was a recipient of a PhD studentship from ARC. We are grateful to F Charlotte, M Tulliez, B Petit, C Chassagne, E Pocachard, E Labouyrie, T Molina and Y Theate for procurement of frozen tissue. We thank K Leroy for technical assistance.

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Correspondence to L Xerri.

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Supplementary Information accompanies the paper on Oncogene website (http://www.nature.com/onc).

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Ballester, B., Ramuz, O., Gisselbrecht, C. et al. Gene expression profiling identifies molecular subgroups among nodal peripheral T-cell lymphomas. Oncogene 25, 1560–1570 (2006). https://doi.org/10.1038/sj.onc.1209178

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