文章基本信息

标题：Activating mutations and translocations in the guanine exchange factor VAV1 in peripheral T-cell lymphomas
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作者：Francesco Abate ; Ana C. da Silva-Almeida ; Sakellarios Zairis 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2017
卷号：114
期号：4
页码：764-769
DOI：10.1073/pnas.1608839114
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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.
关键词：peripheral T-cell lymphoma ; VAV1 ; mutation ; gene fusion