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

[EN]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...

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Detalles Bibliográficos
Autores: Abate, Francesco, da Silva-Almeida, Ana C, Zairis, Sakellarios, Robles Valero, Javier, Couronne, Lucile, Khiabanian, Hossein, Quinn, S Aidan, Kim, Mi-Yeon, Laginestra, Maria Antonella, Kim, Christine, Fiore, Danilo, Bhagat, Govind, Piris, Miguel Angel, Campo, Elias, Lossos, Izidore S, Bernard, Olivier A, Inghirami, Giorgio, Pileri, Stefano, Bustelo, Xosé R., Rabadan, Raul, Ferrando, Adolfo A, Palomero, Teresa
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2017
País:España
Institución:Universidad de Salamanca (USAL)
Repositorio:GREDOS. Repositorio Institucional de la Universidad de Salamanca
OAI Identifier:oai:gredos.usal.es:10366/168600
Acceso en línea:http://hdl.handle.net/10366/168600
Access Level:acceso abierto
Palabra clave:VAV1
Gene fusion
Mutation
Peripheral T-cell lymphoma
Lymphoma
Sequence Deletion
Base Sequence
Humans
Alternative Splicing
Cell Line
Guanine
Proto-Oncogene Proteins c-vav
Jurkat Cells
Amino Acid Sequence
Guanine Nucleotide Exchange Factors
3207.13 Oncología
bio
linfoma
guanina
factores de intercambio de nucleótidos de guanina
deleción de secuencias
humanos
mutación
proteínas protooncogénicas c-vav
secuencia de aminoácidos
secuencia de bases
línea celular
empalme alternativo
células Jurkat
Descripción
Sumario:[EN]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.

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