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

Francesco Abate; Ana C. Da Silva-Almeida; Sakellarios Zairis; Javier Robles-Valero; Lucile Couronne; Hossein Khiabanian; S. Aidan Quinn; Mi Yeon Kim; Maria Antonella Laginestra; Christine Kim; Danilo Fiore; Govind Bhagat; Miguel Angel Piris; Elias Campo; Izidore S. Lossos; Olivier A. Bernard; Giorgio Inghirami; Stefano Pileri; Xosé R. Bustelo; Raul Rabadan; Adolfo A. Ferrando; Teresa Palomero

doi:10.1073/pnas.1608839114

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

Francesco Abate, Ana C. Da Silva-Almeida, Sakellarios Zairis, Javier Robles-Valero, Lucile Couronne, Hossein Khiabanian, S. Aidan Quinn, Mi Yeon Kim, Maria Antonella Laginestra, Christine Kim, Danilo Fiore, Govind Bhagat, Miguel Angel Piris, Elias Campo, Izidore S. Lossos, Olivier A. Bernard, Giorgio Inghirami, Stefano Pileri, Xosé R. Bustelo, Raul RabadanAdolfo A. Ferrando, Teresa Palomero

Résultats de recherche: Contribution à un journal › Article › Revue par des pairs

97 Citations (Scopus)

Résumé

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.

langue originale	Anglais
Pages (de - à)	764-769
Nombre de pages	6
journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	114
Numéro de publication	4
Les DOIs	https://doi.org/10.1073/pnas.1608839114
état	Publié - 24 janv. 2017

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10.1073/pnas.1608839114

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Abate, F., Da Silva-Almeida, A. C., Zairis, S., Robles-Valero, J., Couronne, L., Khiabanian, H., Quinn, S. A., Kim, M. Y., Laginestra, M. A., Kim, C., Fiore, D., Bhagat, G., Piris, M. A., Campo, E., Lossos, I. S., Bernard, O. A., Inghirami, G., Pileri, S., Bustelo, X. R., ... Palomero, T. (2017). 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, 114(4), 764-769. https://doi.org/10.1073/pnas.1608839114

@article{8eafdcb32eb7452783705e17aea8b864,

title = "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 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.",

keywords = "Gene fusion, Mutation, Peripheral T-cell lymphoma, VAV1",

author = "Francesco Abate and {Da Silva-Almeida}, {Ana C.} and Sakellarios Zairis and Javier Robles-Valero and Lucile Couronne and Hossein Khiabanian and Quinn, {S. Aidan} and Kim, {Mi Yeon} and Laginestra, {Maria Antonella} and Christine Kim and Danilo Fiore and Govind Bhagat and Piris, {Miguel Angel} and Elias Campo and Lossos, {Izidore S.} and Bernard, {Olivier A.} and Giorgio Inghirami and Stefano Pileri and Bustelo, {Xos{\'e} R.} and Raul Rabadan and Ferrando, {Adolfo A.} and Teresa Palomero",

note = "Funding Information: This work was supported by National Cancer Institute R01 CA197945-01 (to T.P.), Leukemia & Lymphoma Society (LLS) Awards TRP-6507-17 (to T.P.) and TRP-6163-12 (to A.A.F.), a Herbert Irving Comprehensive Cancer Center interprogrammatic pilot project grant (to A.A.F. and R.R.), and Grant 10007 from the Italian Association for Cancer Research (AIRC) (to S.P.). O.A.B. was supported by Institut National du Cancer (INCa), 2013-1-PL BIO-09, INCa-DGOS-INSERM 6043, equipe labellis{\'e}e Ligue Nationale Contre le Cancer (LNCC), and INCa-DGOS-INSERM 6043. X.R.B.'s work was supported by grants from the Spanish Ministry of Economy and Competitiveness (RD12/0036/0002, SAF2012-31371, and SAF2015-64556-R), Worldwide Cancer Research (14-1248), and Ram{\'o}n Areces Foundation. A.C.d.S.-A. was supported by a Lady Tata Memorial Trust fellowship and an LLS Special Fellowship Award. S.Z. was supported by a TL1 personalized medicine fellowship (5TL1TR000082). L.C. was funded by a postdoctoral grant from Institut Multi Organismes Cancer and INCa. M.-Y.K. was funded by an LLS postdoctoral fellowship.",

year = "2017",

month = jan,

day = "24",

doi = "10.1073/pnas.1608839114",

language = "English",

volume = "114",

pages = "764--769",

journal = "Proceedings of the National Academy of Sciences of the United States of America",

issn = "0027-8424",

number = "4",

}

Abate, F, Da Silva-Almeida, AC, Zairis, S, Robles-Valero, J, Couronne, L, Khiabanian, H, Quinn, SA, Kim, MY, Laginestra, MA, Kim, C, Fiore, D, Bhagat, G, Piris, MA, Campo, E, Lossos, IS, Bernard, OA, Inghirami, G, Pileri, S, Bustelo, XR, Rabadan, R, Ferrando, AA & Palomero, T 2017, '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, VOL. 114, Numéro 4, p. 764-769. https://doi.org/10.1073/pnas.1608839114

Activating mutations and translocations in the guanine exchange factor VAV1 in peripheral T-cell lymphomas. / Abate, Francesco; Da Silva-Almeida, Ana C.; Zairis, Sakellarios et al.
Dans: Proceedings of the National Academy of Sciences of the United States of America, Vol 114, Numéro 4, 24.01.2017, p. 764-769.

Résultats de recherche: Contribution à un journal › Article › Revue par des pairs

TY - JOUR

T1 - Activating mutations and translocations in the guanine exchange factor VAV1 in peripheral T-cell lymphomas

AU - Abate, Francesco

AU - Da Silva-Almeida, Ana C.

AU - Zairis, Sakellarios

AU - Robles-Valero, Javier

AU - Couronne, Lucile

AU - Khiabanian, Hossein

AU - Quinn, S. Aidan

AU - Kim, Mi Yeon

AU - Laginestra, Maria Antonella

AU - Kim, Christine

AU - Fiore, Danilo

AU - Bhagat, Govind

AU - Piris, Miguel Angel

AU - Campo, Elias

AU - Lossos, Izidore S.

AU - Bernard, Olivier A.

AU - Inghirami, Giorgio

AU - Pileri, Stefano

AU - Bustelo, Xosé R.

AU - Rabadan, Raul

AU - Ferrando, Adolfo A.

AU - Palomero, Teresa

N1 - Funding Information: This work was supported by National Cancer Institute R01 CA197945-01 (to T.P.), Leukemia & Lymphoma Society (LLS) Awards TRP-6507-17 (to T.P.) and TRP-6163-12 (to A.A.F.), a Herbert Irving Comprehensive Cancer Center interprogrammatic pilot project grant (to A.A.F. and R.R.), and Grant 10007 from the Italian Association for Cancer Research (AIRC) (to S.P.). O.A.B. was supported by Institut National du Cancer (INCa), 2013-1-PL BIO-09, INCa-DGOS-INSERM 6043, equipe labellisée Ligue Nationale Contre le Cancer (LNCC), and INCa-DGOS-INSERM 6043. X.R.B.'s work was supported by grants from the Spanish Ministry of Economy and Competitiveness (RD12/0036/0002, SAF2012-31371, and SAF2015-64556-R), Worldwide Cancer Research (14-1248), and Ramón Areces Foundation. A.C.d.S.-A. was supported by a Lady Tata Memorial Trust fellowship and an LLS Special Fellowship Award. S.Z. was supported by a TL1 personalized medicine fellowship (5TL1TR000082). L.C. was funded by a postdoctoral grant from Institut Multi Organismes Cancer and INCa. M.-Y.K. was funded by an LLS postdoctoral fellowship.

PY - 2017/1/24

Y1 - 2017/1/24

N2 - 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.

AB - 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.

KW - Gene fusion

KW - Mutation

KW - Peripheral T-cell lymphoma

KW - VAV1

UR - http://www.scopus.com/inward/record.url?scp=85010955894&partnerID=8YFLogxK

U2 - 10.1073/pnas.1608839114

DO - 10.1073/pnas.1608839114

M3 - Article

C2 - 28062691

AN - SCOPUS:85010955894

SN - 0027-8424

VL - 114

SP - 764

EP - 769

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 4

ER -