Molecular pathogenesis of cutaneous lymphoma-Future directions

Exp Dermatol. 2020 Nov;29(11):1062-1068. doi: 10.1111/exd.14211. Epub 2020 Oct 28.

Abstract

The pathogenesis of cutaneous T-cell lymphomas is not clear. In recent years, the genetic changes in CTCL were explored. The detected mutations showed a great deal of heterogeneity between individual patients. The studies documented various copy number variations (CNV) and single nucleotide variations (SNV) in multiple genes involved in multiple signalling pathways. Recurrently mutated signalling pathways include JAK-STAT, MAPK, T-cell receptor, TNF receptor and NFκB signalling. In the period between 2018 and today, additional studies towards the genetic changes in CTCL were carried out. Genetic changes in gamma delta T-cell lymphoma are also shown in genes of the JAK-STAT, MAPK, MYC and chromatin signalling pathways. These studies might indicate a shift away from targeted sequencing approaches towards whole-genome sequencing. This approach demands additional resources in terms of funding but has the advantage of finding mutations in non-coding regions. These mutations were neglected for a long time, but as shown in contemporary research these regions harbour highly recurrent mutations affecting gene expression and regulation. Nevertheless, the detection of specific molecular changes in known pathways enables considerations for targeted therapies.

Keywords: cutaneous T-cell lymphoma; genetic landscape; targeted therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor
  • Biomedical Research
  • DNA Copy Number Variations
  • Genetic Variation*
  • Humans
  • Lymphoma, T-Cell, Cutaneous / drug therapy
  • Lymphoma, T-Cell, Cutaneous / genetics*
  • Mutation
  • Polymorphism, Single Nucleotide
  • Signal Transduction / genetics*
  • Skin Neoplasms / drug therapy
  • Skin Neoplasms / genetics*

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor