Genetics of Cutaneous T Cell Lymphoma: From Bench to Bedside

William E. Damsky, Jaehyuk Choi*

*Corresponding author for this work

Research output: Contribution to journalReview article

21 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article number33
JournalCurrent Treatment Options in Oncology
Volume17
Issue number7
DOIs
StatePublished - Jul 1 2016

Fingerprint

Cutaneous T-Cell Lymphoma
T-Lymphocytes
Neoplasms
Precision Medicine
Skin
Mutation
Endonucleases
Mutagens
T-Cell Antigen Receptor
Non-Hodgkin's Lymphoma
Genetic Recombination
Therapeutics
Biomarkers
Lymph Nodes
Radiation
Apoptosis
Genes

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Pharmacology (medical)

Cite this

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title = "Genetics of Cutaneous T Cell Lymphoma: From Bench to Bedside",
abstract = "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.",
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Genetics of Cutaneous T Cell Lymphoma : From Bench to Bedside. / Damsky, William E.; Choi, Jaehyuk.

In: Current Treatment Options in Oncology, Vol. 17, No. 7, 33, 01.07.2016.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Genetics of Cutaneous T Cell Lymphoma

T2 - From Bench to Bedside

AU - Damsky, William E.

AU - Choi, Jaehyuk

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N2 - 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.

AB - 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.

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