Title | Mutational analysis of PRDM1 indicates a tumor-suppressor role in diffuse large B-cell lymphomas. |
Publication Type | Journal Article |
Year of Publication | 2006 |
Authors | Tam W, Gomez M, Chadburn A, Lee JW, Chan WC, Knowles DM |
Journal | Blood |
Volume | 107 |
Issue | 10 |
Pagination | 4090-100 |
Date Published | 2006 May 15 |
ISSN | 0006-4971 |
Keywords | Amino Acid Sequence, Base Sequence, Cell Line, Tumor, Cell Nucleus, DNA Primers, Exons, Genes, Tumor Suppressor, Humans, Introns, Lymphoma, B-Cell, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Non-Hodgkin, Molecular Sequence Data, Polymerase Chain Reaction, Positive Regulatory Domain I-Binding Factor 1, Repressor Proteins, Transcription Factors |
Abstract | 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. |
DOI | 10.1182/blood-2005-09-3778 |
Alternate Journal | Blood |
PubMed ID | 16424392 |
Related Faculty:
Amy Chadburn, M.D.