Mutational analysis of PRDM1 indicates a tumor-suppressor role in diffuse large B-cell lymphomas Academic Article uri icon


MeSH Major

  • Lymphoma, B-Cell
  • Lymphoma, Large B-Cell, Diffuse
  • Lymphoma, Non-Hodgkin
  • Repressor Proteins
  • Transcription Factors


  • The PR (PRDI-BF1-RIZ) domain zinc finger protein 1 (PRDM1) is a transcription repressor with a pivotal role in plasma-cell differentiation. We identified clonal inactivating mutations in PRDM1 in the diffuse large B-cell lymphoma (DLBCL) cell line OCI-Ly3 and in 8 of 35 de novo clinical DLBCL samples. The mutational spectrum consists predominantly (7 cases) of single-nucleotide mutations affecting consensus splice donor sites, some of which are recurrent, that lead to splicing aberrations and premature translation termination. In 2 of these cases, point mutations appear to be caused by RNA editing with G-to-A and U-to-G conversions. Other mutations include frame-shift deletion and chromosomal inversion. Except for one mutant, which may act as a dominant-negative, all mutations are associated with either deletion or silencing of the paired PRDM1 allele. This study identifies PRDM1 inactivation as a recurrent genetic defect in DLBCL cells and establishes PRDM1 as a potential tumor suppressor gene in DLBCL. Moreover, it implies inhibition of terminal differentiation as a pathogenetic pathway in DLBCL, particularly for the activated B-cell-like DLBCL. It also demonstrates for the first time the potential role of RNA editing in lymphomagenesis.

publication date

  • May 15, 2006



  • Academic Article



  • eng

Digital Object Identifier (DOI)

  • 10.1182/blood-2005-09-3778

PubMed ID

  • 16424392

Additional Document Info

start page

  • 4090

end page

  • 100


  • 107


  • 10