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Activating mutations and translocations in the guanine exchange factor VAV1 in peripheral T-cell lymphomas.
- 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]
- Subjects :
- *T-cell lymphoma
*LYMPHOMAS
*RNA sequencing
*GENE fusion
*T cells
*CARCINOGENESIS
Subjects
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