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

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

Proceedings of the National Academy of Sciences - PNAS, 2017-01, Vol.114 (4), p.764-769 [Periódico revisado por pares]

United States: National Academy of Sciences

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Título:
Activating mutations and translocations in the guanine exchange factor VAV1 in peripheral T-cell lymphomas
Autor: 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
Assuntos: Alternative Splicing - genetics ; Amino Acid Sequence ; Base Sequence ; Biological Sciences ; Cell Line, Tumor ; Cèl·lules T ; Genes ; Genetics ; Gens ; Guanine - metabolism ; Guanine Nucleotide Exchange Factors - genetics ; Humans ; Jurkat Cells ; Lymphocytes ; Lymphoma ; Lymphoma, T-Cell, Peripheral - genetics ; Medical prognosis ; Mutació (Biologia) ; Mutation (Biology) ; Mutation - genetics ; Pathogenesis ; Proto-Oncogene Proteins c-vav - genetics ; Sequence Deletion - genetics ; T cells ; Translocation, Genetic - genetics
É parte de: Proceedings of the National Academy of Sciences - PNAS, 2017-01, Vol.114 (4), p.764-769
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Edited by Seishi Ogawa, Kyoto University, Kyoto, Japan, and accepted by Editorial Board Member Tadatsugu Taniguchi December 5, 2016 (received for review June 3, 2016)
1F.A. and A.C.d.S.-A. contributed equally to this work.
Author contributions: H.K., X.R.B., R.R., A.A.F., and T.P. designed research; A.C.d.S.-A., J.R.-V., L.C., M.-Y.K., C.K., and T.P. performed research; M.A.L., D.F., G.B., M.A.P., E.C., I.S.L., O.A.B., G.I., and S.P. contributed new reagents/analytic tools; F.A., A.C.d.S.-A., S.Z., H.K., S.A.Q., X.R.B., R.R., A.A.F., and T.P. analyzed data; and A.A.F. and T.P. wrote the paper.
Descrição: 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.
Editor: United States: National Academy of Sciences
Idioma: Inglês

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

United States: National Academy of Sciences

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