Genetic alterations affecting GTPases and T-cell receptor signaling in peripheral T-cell lymphomas

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4 Citations (Scopus)

Abstract

Peripheral T-cell lymphomas (PTCLs) are rare, heterogeneous tumors with poor response to standard therapy and few targeted treatments available. The identification of mutations in the T-cell receptor (TCR) signaling pathway that either directly or indirectly affect Ras- and Rho-family GTPases is an emerging theme across PTCL subtypes. This review summarizes the role of GTPases in TCR signaling and highlights the constellation of mutations in this pathway among PTCLs. In particular, focus is given to the functional impact of the mutations and opportunities for targeted therapy. These mutations include activating mutations and gene fusions involving the guanine nucleotide exchange factor, VAV1, as well as activating and dominant negative mutations in the GTPases KRAS and RHOA, respectively. In addition to mutations directly affecting the GTPase pathway, TCR signaling mutations indirectly affecting Ras- and Rho-family GTPases involving genes such as CD28, FYN, LCK, and PLCG1 are also reviewed.

Original languageEnglish (US)
Pages (from-to)33-39
Number of pages7
JournalSmall GTPases
Volume10
Issue number1
DOIs
StatePublished - Jan 2 2019

Fingerprint

Peripheral T-Cell Lymphoma
T-cells
GTP Phosphohydrolases
T-Cell Antigen Receptor
Mutation
rho GTP-Binding Proteins
Genes
Guanine Nucleotide Exchange Factors
Tumors
Fusion reactions
Gene Fusion

Keywords

  • fusion protein
  • GTPase
  • mutation
  • peripheral T-cell lymphoma
  • RAC1
  • RHOA
  • T cell signaling
  • VAV1

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

Cite this

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title = "Genetic alterations affecting GTPases and T-cell receptor signaling in peripheral T-cell lymphomas",
abstract = "Peripheral T-cell lymphomas (PTCLs) are rare, heterogeneous tumors with poor response to standard therapy and few targeted treatments available. The identification of mutations in the T-cell receptor (TCR) signaling pathway that either directly or indirectly affect Ras- and Rho-family GTPases is an emerging theme across PTCL subtypes. This review summarizes the role of GTPases in TCR signaling and highlights the constellation of mutations in this pathway among PTCLs. In particular, focus is given to the functional impact of the mutations and opportunities for targeted therapy. These mutations include activating mutations and gene fusions involving the guanine nucleotide exchange factor, VAV1, as well as activating and dominant negative mutations in the GTPases KRAS and RHOA, respectively. In addition to mutations directly affecting the GTPase pathway, TCR signaling mutations indirectly affecting Ras- and Rho-family GTPases involving genes such as CD28, FYN, LCK, and PLCG1 are also reviewed.",
keywords = "fusion protein, GTPase, mutation, peripheral T-cell lymphoma, RAC1, RHOA, T cell signaling, VAV1",
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T1 - Genetic alterations affecting GTPases and T-cell receptor signaling in peripheral T-cell lymphomas

AU - Luchtel, Rebecca

AU - Razidlo, Gina

AU - Feldman, Andrew L

PY - 2019/1/2

Y1 - 2019/1/2

N2 - Peripheral T-cell lymphomas (PTCLs) are rare, heterogeneous tumors with poor response to standard therapy and few targeted treatments available. The identification of mutations in the T-cell receptor (TCR) signaling pathway that either directly or indirectly affect Ras- and Rho-family GTPases is an emerging theme across PTCL subtypes. This review summarizes the role of GTPases in TCR signaling and highlights the constellation of mutations in this pathway among PTCLs. In particular, focus is given to the functional impact of the mutations and opportunities for targeted therapy. These mutations include activating mutations and gene fusions involving the guanine nucleotide exchange factor, VAV1, as well as activating and dominant negative mutations in the GTPases KRAS and RHOA, respectively. In addition to mutations directly affecting the GTPase pathway, TCR signaling mutations indirectly affecting Ras- and Rho-family GTPases involving genes such as CD28, FYN, LCK, and PLCG1 are also reviewed.

AB - Peripheral T-cell lymphomas (PTCLs) are rare, heterogeneous tumors with poor response to standard therapy and few targeted treatments available. The identification of mutations in the T-cell receptor (TCR) signaling pathway that either directly or indirectly affect Ras- and Rho-family GTPases is an emerging theme across PTCL subtypes. This review summarizes the role of GTPases in TCR signaling and highlights the constellation of mutations in this pathway among PTCLs. In particular, focus is given to the functional impact of the mutations and opportunities for targeted therapy. These mutations include activating mutations and gene fusions involving the guanine nucleotide exchange factor, VAV1, as well as activating and dominant negative mutations in the GTPases KRAS and RHOA, respectively. In addition to mutations directly affecting the GTPase pathway, TCR signaling mutations indirectly affecting Ras- and Rho-family GTPases involving genes such as CD28, FYN, LCK, and PLCG1 are also reviewed.

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KW - RAC1

KW - RHOA

KW - T cell signaling

KW - VAV1

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