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Peripheral T-cell lymphomas (PTCLs) (i.e. neoplasias derived from mature T and NK cells) are a heterogeneous group of rare diseases, accounting for less than 10% of all lymphomas. These cancers pose several challenges: most exhibit resistance to classical polychemotherapy regimens and have a poor prognosis; their pathological diagnosis of PTCLs is often difficult, and the genetic alterations underlying their pathogenesis are largely unknown; and research in the field of PTCLs has been hampered by the absence of cell lines representative of the major entities, and the lack of good animal models. (1) Our works over the past few years have contributed to the understanding of the pathobiology of some of these disease entities (2-4); in particular we showed that angioimmunoblastic T-cell lymphoma (AITL), which is one of the most common disease entities, is derived from a peculiar T-cell subpopulation, namely follicular helper T cells, and our studies highlighted some overlap between AITL and another entity named PTCL, not otherwise specified (PTCL, NOS).(2,5) The molecular mechanisms driving TFH oncogenic transformation remain largely unknown.(6-8)

Our ongoing project aiming at gaining novel insights into the molecular classification of PTCLs, relies on an integrated strategy analysing genomic alterations, mRNA and mi-RNA profiles, and epigenetic alterations of a large collection of PTCLs with frozen tumor samples (approx. 300 cases), collected in the frame of a multicentric consortium (France, Belgium and Switzerland). A large number of reactive lymphoid tissues and various sorted T-cell populations are also used as controls for comparison. We expect that the combination of overall gene expression patterns and (epi)genetics will improve their biomolecular classification and should identify clinical traits that will allow therapeutic stratification. Specifically, the following questions are being addressed:

• What are the oncogenic mechanisms underlying PTCL pathogenesis?
• Can molecular profiles improve the classification of PTCLs?
• Are molecular signatures associated with distinct clinical traits, prognoses and/or response to treatment?
• Can these molecular studies help to characterize new potential therapeutic targets and be used as a rationale for specific therapies?