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Genetic and epigenetic insights into cutaneous T-cell lymphoma.

Primary cutaneous T-cell lymphomas (CTCL) constitute a heterogeneous group of non-Hodgkin T-cell lymphomas that present in the skin. In recent years significant progress has been made in the understanding of the pathogenesis of CTCL. Progress in CTCL classifications combined with technical advances, in particular next generation sequencing (NGS), enabled a more detailed analysis of the genetic and epigenetic landscape and transcriptional changes in clearly defined diagnostic entities. These studies not only demonstrated extensive heterogeneity between different CTCL subtypes but also identified recurrent alterations that are highly characteristic for diagnostic subgroups of CTCL. The identified alterations in particular involve epigenetic remodelling, cell cycle regulation, and the constitutive activation of targetable, oncogenic pathways. In this respect, aberrant JAK-STAT signaling is a recurrent theme, however not universal for all CTCL and with seemingly different underlaying causes in different entities. A number of the mutated genes identified are potentially actionable targets for the development of novel therapeutic strategies. Moreover, these studies have produced an enormous amount of information that will be critically important for the further development of improved diagnostic and prognostic biomarkers that can assist in the clinical management of CTCL patients. In the present review the main findings of these studies in relation to their functional impact on the malignant transformation process are discussed for different subtypes of CTCL.