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

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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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

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spelling	Activating mutations and translocations in the guanine exchange factor VAV1 in peripheral T-cell lymphomasAbate, Francescoda Silva-Almeida, Ana CZairis, SakellariosRobles Valero, JavierCouronne, LucileKhiabanian, HosseinQuinn, S AidanKim, Mi-YeonLaginestra, Maria AntonellaKim, ChristineFiore, DaniloBhagat, GovindPiris, Miguel AngelCampo, EliasLossos, Izidore SBernard, Olivier AInghirami, GiorgioPileri, StefanoBustelo, Xosé R.Rabadan, RaulFerrando, Adolfo APalomero, TeresaVAV1Gene fusionMutationPeripheral T-cell lymphomaLymphomaSequence DeletionMutationBase SequenceHumansAlternative SplicingCell LineGuanineProto-Oncogene Proteins c-vavJurkat CellsAmino Acid SequenceGuanine Nucleotide Exchange Factors3207.13 Oncologíabiolinfomaguaninafactores de intercambio de nucleótidos de guaninadeleción de secuenciashumanosmutaciónproteínas protooncogénicas c-vavsecuencia de aminoácidossecuencia de baseslínea celularempalme alternativocélulas Jurkat[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.National Academy of Sciences (NAS) de EE.UU202620262017info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10366/168600reponame:GREDOS. Repositorio Institucional de la Universidad de Salamancainstname:Universidad de Salamanca (USAL)InglésSpanish Ministry of Economy and Competitiveness (RD12/0036/0002, SAF2012-31371, and SAF2015-64556-RAttribution-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nd/4.0/info:eu-repo/semantics/openAccessoai:gredos.usal.es:10366/1686002026-06-07T06:28:51Z
dc.title.none.fl_str_mv	Activating mutations and translocations in the guanine exchange factor VAV1 in peripheral T-cell lymphomas
title	Activating mutations and translocations in the guanine exchange factor VAV1 in peripheral T-cell lymphomas
spellingShingle	Activating mutations and translocations in the guanine exchange factor VAV1 in peripheral T-cell lymphomas Abate, Francesco VAV1 Gene fusion Mutation Peripheral T-cell lymphoma Lymphoma Sequence Deletion Mutation 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
title_short	Activating mutations and translocations in the guanine exchange factor VAV1 in peripheral T-cell lymphomas
title_full	Activating mutations and translocations in the guanine exchange factor VAV1 in peripheral T-cell lymphomas
title_fullStr	Activating mutations and translocations in the guanine exchange factor VAV1 in peripheral T-cell lymphomas
title_full_unstemmed	Activating mutations and translocations in the guanine exchange factor VAV1 in peripheral T-cell lymphomas
title_sort	Activating mutations and translocations in the guanine exchange factor VAV1 in peripheral T-cell lymphomas
dc.creator.none.fl_str_mv	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
author	Abate, Francesco
author_facet	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
author_role	author
author2	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
author2_role	author author author author author author author author author author author author author author author author author author author author author
dc.subject.none.fl_str_mv	VAV1 Gene fusion Mutation Peripheral T-cell lymphoma Lymphoma Sequence Deletion Mutation 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
topic	VAV1 Gene fusion Mutation Peripheral T-cell lymphoma Lymphoma Sequence Deletion Mutation 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
description	[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.
publishDate	2017
dc.date.none.fl_str_mv	2017 2026 2026
dc.type.none.fl_str_mv	info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion
format	article
status_str	publishedVersion
dc.identifier.none.fl_str_mv	http://hdl.handle.net/10366/168600
url	http://hdl.handle.net/10366/168600
dc.language.none.fl_str_mv	Inglés
language_invalid_str_mv	Inglés
dc.relation.none.fl_str_mv	Spanish Ministry of Economy and Competitiveness (RD12/0036/0002, SAF2012-31371, and SAF2015-64556-R
dc.rights.none.fl_str_mv	Attribution-NoDerivatives 4.0 Internacional http://creativecommons.org/licenses/by-nd/4.0/ info:eu-repo/semantics/openAccess
rights_invalid_str_mv	Attribution-NoDerivatives 4.0 Internacional http://creativecommons.org/licenses/by-nd/4.0/
eu_rights_str_mv	openAccess
dc.publisher.none.fl_str_mv	National Academy of Sciences (NAS) de EE.UU
publisher.none.fl_str_mv	National Academy of Sciences (NAS) de EE.UU
dc.source.none.fl_str_mv	reponame:GREDOS. Repositorio Institucional de la Universidad de Salamanca instname:Universidad de Salamanca (USAL)
instname_str	Universidad de Salamanca (USAL)
reponame_str	GREDOS. Repositorio Institucional de la Universidad de Salamanca
collection	GREDOS. Repositorio Institucional de la Universidad de Salamanca
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score	15,198674

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

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