| Literature DB >> 28062691 |
Francesco Abate1, Ana C da Silva-Almeida2, Sakellarios Zairis1, Javier Robles-Valero3, Lucile Couronne4,5,6, Hossein Khiabanian1, S Aidan Quinn2, Mi-Yeon Kim2, Maria Antonella Laginestra7, Christine Kim2, Danilo Fiore8, Govind Bhagat9, Miguel Angel Piris10, Elias Campo11, Izidore S Lossos12,13, Olivier A Bernard14,15,16, Giorgio Inghirami8, Stefano Pileri7, Xosé R Bustelo3,17, Raul Rabadan18,19, Adolfo A Ferrando20,9,21, Teresa Palomero20,9.
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.Entities:
Keywords: VAV1; gene fusion; mutation; peripheral T-cell lymphoma
Mesh：
Substances：
Year: 2017 PMID： 28062691 PMCID： PMC5278460 DOI： 10.1073/pnas.1608839114
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 11.205