Activating mutations and translocations in the guanine exchange factor VAV1 in peripheral T-cell lymphomas.

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of non-Hodgkin lymphomas frequently associated with poor prognosis and for which genetic mechanisms of transformation remain incompletely understood. Using RNA sequencing and targeted sequencing, here we identify a recurrent in-frame dele...

Full description

Bibliographic Details
Authors: Abate, Francesco, Silva-Almeida, Ana C. da, Zairis, Sakellarios, Robles Valero, Javier, Couronne, Lucile, Khiabanian, Hossein, Quinn, S. Aidan, Kim, Mi-Yeon, Laginestra, M.Antonella, Kim, Christine, Fiore, Danilo, Bhagat, Govind, Piris, Miguel A., Campo Güerri, Elias, Lossos, Izidore S., Bernard, Olivier A., Inghirami, Giorgio, Pileri, Stefano Aldo, Bustelo, Xosé R., Rabadán, Raul, Ferrando, Adolfo A., Palomero, Teresa
Format: article
Status:Published version
Publication Date:2017
Country:España
Institution:Universidad de Barcelona
Repository:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/132739
Online Access:https://hdl.handle.net/2445/132739
Access Level:Open access
Keyword:Mutació (Biologia)
Gens
Cèl·lules T
Mutation (Biology)
Genes
T cells
Description
Summary:Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of non-Hodgkin lymphomas frequently associated with poor prognosis and for which genetic mechanisms of transformation remain incompletely understood. Using RNA sequencing and targeted sequencing, here we identify a recurrent in-frame deletion (VAV1 Δ778-786) generated by a focal deletion-driven alternative splicing mechanism as well as novel VAV1 gene fusions (VAV1-THAP4, VAV1-MYO1F, and VAV1-S100A7) in PTCL. Mechanistically these genetic lesions result in increased activation of VAV1 catalytic-dependent (MAPK, JNK) and non-catalytic-dependent (nuclear factor of activated T cells, NFAT) VAV1 effector pathways. These results support a driver oncogenic role for VAV1 signaling in the pathogenesis of PTCL.

Similar Items