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Activating mutations and translocations in the guanine exchange factor VAV1 in peripheral T-cell lymphomas.
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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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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. Activating mutations and translocations in the guanine exchange factor VAV1 in peripheral T-cell lymphomas.. _Proceedings of the National Academy of Sciences of the United States of America - PNAS_. 2017. Vol. 114, núm. 4, pàgs. 764-9. [consulta: 21 de gener de 2026]. ISSN: 0027-8424. [Disponible a: https://hdl.handle.net/2445/132739]