Activating mutations and translocations in the guanine exchange factor VAV1 in peripheral T-cell lymphomas Academic Article uri icon


MeSH Major

  • Biomarkers, Tumor
  • Exome
  • Lymphoma, B-Cell, Marginal Zone
  • Mutation
  • Receptor, Notch2
  • Receptor-Like Protein Tyrosine Phosphatases, Class 2
  • Splenic Neoplasms


  • 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.

publication date

  • January 24, 2017



  • Academic Article



  • eng

PubMed Central ID

  • PMC5278460

Digital Object Identifier (DOI)

  • 10.1073/pnas.1608839114

PubMed ID

  • 28062691

Additional Document Info

start page

  • 764

end page

  • 769


  • 114


  • 4