Translational Research in Peripheral T-Cell Lymphomas

Background Peripheral T-cell lymphomas (PTCL) are a heterogeneous group of rare lymphoid malignancies. With current treatment options, the majority of patients do not achieve remission or experience relapse after completion of therapy, generally with dismal outcome [1-4]. Mechanisms of progression and relapse remain elusive and predictive biomarkers do not exist, precluding clinical progress. Hypothesis We hypothesize that utilizing a unique collection of clinically annotated samples from multiple European trials and registries for detailed pathologic assessment and comprehensive characterization of the (epi-) genetic landscape will unravel pivotal mechanisms determining the unique biology and clinical behavior of PTCL. Aims Aim 1: Collect a clinically annotated, comprehensively characterized and centrally reviewed sample collection of PTCL. Aim 2: Perform a comprehensive genetic and epigenetic characterization and identify prognostic (epi-) genetic biomarkers. Aim 3: Identify molecular targets and develop novel therapeutic strategies. Methods This study will be based on biopsy samples of patients treated in prospective European clinical trials and from population-based cohorts that are collected via the national pathology reference centers. Whole exome sequencing, genome-wide DNA methylation profiling and targeted sequencing results will be correlated with clinical parameters, including progression and outcome. (Epi-) Genetic alterations will be addressed with drug screening assays in pre-clinical models and ex vivo in primary PTCL samples. Expected results & impact This study will provide a comprehensively characterized catalogue of clinically annotated samples across the major subtypes of PTCL. The integrated analysis of (epi-) genetic alterations will elucidate pathogenic mechanisms and the correlation with clinical endpoints will provide insight in prognostic biomarkers. Finally, novel therapeutic strategies will be explored on the basis of these data.