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

Authors :
Abate, Francesco
Silva-Almeida, Ana C. da
Zairis, Sakellarios
Robles-Valero, Javier
Couronne, Lucile
Khiabanian, Hossein
Quinn, S. Aidan
Mi-Yeon Kim
Laginestra, Maria Antonella
Christine Kim
Fiore, Danilo
Bhagat, Govind
Piris, Miguel Angel
Campo, Elias
Lossos, Izidore S.
Bernard, Olivier A.
Inghirami, Giorgio
Pileri, Stefano
Bustelo, Xosé R.
Rabadan, Raul
Source :
Proceedings of the National Academy of Sciences of the United States of America. 1/24/2017, Vol. 114 Issue 4, p164-169. 6p.
Publication Year :
2017

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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00278424
Volume :
114
Issue :
4
Database :
Academic Search Index
Journal :
Proceedings of the National Academy of Sciences of the United States of America
Publication Type :
Academic Journal
Accession number :
121029757
Full Text :
https://doi.org/10.1073/pnas.1608839114