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 GTPasesKRASandRHOA, respectively. In addition to mutations directly affecting the GTPase pathway, TCR signaling mutations indirectly affecting Ras- and Rho-family GTPases involving genes such asCD28, FYN, LCK, andPLCG1are also reviewed.
authors.affiliation: a Department of Laboratory Medicine and Pathology , Mayo Clinic , Rochester , MN , USA.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Boddicker
authors.affiliation: b Center for Basic Research in Digestive Diseases, Division of Gastroenterology & Hepatology, Mayo Clinic , Rochester , MN , USA.|c Department of Biochemistry and Molecular Biology , Mayo Clinic , Rochester , MN , USA.
authors.forename: Gina L
authors.identifier: 0000-0002-9042-2738
authors.initials: GL
authors.lastname: Razidlo
authors.affiliation: a Department of Laboratory Medicine and Pathology , Mayo Clinic , Rochester , MN , USA.
authors.forename: Andrew L
authors.identifier: 0000-0001-5009-4808
authors.initials: AL
authors.lastname: Feldman
mesh_terms: D020558:GTP Phosphohydrolases / Q000235:genetics*; D006801:Humans; D016411:Lymphoma, T-Cell, Peripheral / Q000235:genetics* / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D015398:Signal Transduction
chemical_list: D011948:Receptors, Antigen, T-Cell; D020558:GTP Phosphohydrolases
keywords: GTPase; RAC1; RHOA; T cell signaling; VAV1; fusion protein; mutation; peripheral T-cell lymphoma