| Title | Activating mutations and translocations in the guanine exchange factor VAV1 in peripheral T-cell lymphomas. |
| Publication Type | Journal Article |
| Year of Publication | 2017 |
| Authors | Abate F, da Silva-Almeida AC, Zairis S, Robles-Valero J, Couronne L, Khiabanian H, S Quinn A, Kim M-Y, Laginestra MAntonella, Kim C, Fiore D, Bhagat G, Piris MAngel, Campo E, Lossos IS, Bernard OA, Inghirami G, Pileri S, Bustelo XR, Rabadan R, Ferrando AA, Palomero T |
| Journal | Proc Natl Acad Sci U S A |
| Volume | 114 |
| Issue | 4 |
| Pagination | 764-769 |
| Date Published | 2017 01 24 |
| ISSN | 1091-6490 |
| Keywords | Alternative Splicing, Amino Acid Sequence, Base Sequence, Cell Line, Tumor, Guanine, Guanine Nucleotide Exchange Factors, Humans, Jurkat Cells, Lymphoma, T-Cell, Peripheral, Mutation, Proto-Oncogene Proteins c-vav, Sequence Deletion, Translocation, Genetic |
| 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. |
| DOI | 10.1073/pnas.1608839114 |
| Alternate Journal | Proc Natl Acad Sci U S A |
| PubMed ID | 28062691 |
| PubMed Central ID | PMC5278460 |
| Grant List | 14-1248 / / Worldwide Cancer Research / United Kingdom R01 CA197945 / CA / NCI NIH HHS / United States T32 GM007367 / GM / NIGMS NIH HHS / United States TL1 TR000082 / TR / NCATS NIH HHS / United States |
Related Faculty:
Giorgio Inghirami, M.D.