Genetics of Cutaneous T Cell Lymphoma: From Bench to Bedside

  • William E. Damsky
  • Jaehyuk ChoiEmail author
Skin Cancer (BY Kwong, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Skin Cancer

Opinion statement

Cutaneous T cell lymphomas (CTCLs) are non-Hodgkin lymphomas of skin homing T cells. Although early-stage disease may be limited to the skin, tumor cells in later stage disease can populate the blood, the lymph nodes, and the visceral organs. Unfortunately, there are few molecular biomarkers to guide diagnosis, staging, or treatment of CTCL. Diagnosis of CTCL can be challenging and requires the synthesis of clinical findings, histopathology, and T cell clonality studies; however, none of these tests are entirely sensitive or specific for CTCL. Treatment of CTCL is often empiric and is not typically based on specific molecular alterations, as is common in other cancers. In part, limitations in diagnosis and treatment selection reflect the limited insight into the genetic basis of CTCL. Recent next-generation sequencing has revolutionized our understanding of the mutational landscape in this disease. These analyses have uncovered ultraviolet radiation and recombination activating gene (RAG) endonucleases as important mutagens. Furthermore, these studies have revealed potentially targetable oncogenic mutations in the T cell receptor complex, NF-κB, and JAK-STAT signaling pathways. Collectively, these somatic mutations drive lymphomagenesis via cancer-promoting changes in proliferation, apoptosis, and T cell effector function. We expect that these genetic findings will launch a new era of precision medicine in CTCL.


Cutaneous T cell lymphoma CTCL Mycosis fungoides Next-generation sequencing JAK-STAT NF-κB Bortezomib Tofacitinib Ruxolitinib 


Compliance with Ethical Standards

Conflict of Interest

William E. Damsky and Jaehyuk Choi declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Department of DermatologyYale University School of MedicineNew HavenUSA
  2. 2.Department of Dermatology and Department of Biochemistry and Molecular GeneticsNorthwestern University Feinberg School of Medicine, Robert H Lurie Medical Research CenterChicagoUSA

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