High resolution integrated genomic analyses of distinct clinical entities within cutaneous T-cell lymphomas

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. In particular accurate classification of CTCL combined with molecular analysis (including next generation sequencing), enabled a more detailed analysis of the genetic and epigenetic landscape and transcriptional changes in clearly defined diagnostic entities. We recently were the first to publish high-resolution integrated (DNA/RNA) genome-wide studies focusing on the characterization of structural variations (SVs) and copy number alterations (CNAs) in cohorts exclusively formed by patients with tumor stage mycosis fungoides or Sézary syndrome. Here we will present comparable studies based on other CTCL entities and a comprehensive description of genetic alterations (i.e. genomic rearrangements, CNAs and small-scale mutations) with pathogenic relevance for different subtypes of CTCL. These data not only confirm a crucial role for aberrant JAK-STAT signalling in CTCL, but also show distinct mechanisms in separate clinical entities suggesting that different therapeutic approaches are warranted. 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. In particular accurate classification of CTCL combined with molecular analysis (including next generation sequencing), enabled a more detailed analysis of the genetic and epigenetic landscape and transcriptional changes in clearly defined diagnostic entities. We recently were the first to publish high-resolution integrated (DNA/RNA) genome-wide studies focusing on the characterization of structural variations (SVs) and copy number alterations (CNAs) in cohorts exclusively formed by patients with tumor stage mycosis fungoides or Sézary syndrome. Here we will present comparable studies based on other CTCL entities and a comprehensive description of genetic alterations (i.e. genomic rearrangements, CNAs and small-scale mutations) with pathogenic relevance for different subtypes of CTCL. These data not only confirm a crucial role for aberrant JAK-STAT signalling in CTCL, but also show distinct mechanisms in separate clinical entities suggesting that different therapeutic approaches are warranted.