Dataset Information

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

ABSTRACT: 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 ?778-786) 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.

SUBMITTER: Abate F

PROVIDER: S-EPMC5278460 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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

Abate Francesco F da Silva-Almeida Ana C AC Zairis Sakellarios S Robles-Valero Javier J Couronne Lucile L Khiabanian Hossein H Quinn S Aidan SA Kim Mi-Yeon MY Laginestra Maria Antonella MA Kim Christine C Fiore Danilo D Bhagat Govind G Piris Miguel Angel MA Campo Elias E Lossos Izidore S IS Bernard Olivier A OA Inghirami Giorgio G Pileri Stefano S Bustelo Xosé R XR Rabadan Raul R Ferrando Adolfo A AA Palomero Teresa T

Proceedings of the National Academy of Sciences of the United States of America 20170106 4

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 gen ...[more]

PMID: 28062691

Dataset Information

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

Publications

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

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