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Blood, 15 May 2006, Vol. 107, No. 10, pp. 4090-4100. Prepublished online as a Blood First Edition Paper on January 19, 2006; DOI 10.1182/blood-2005-09-3778. This Article Full Text (PDF) All Versions of this Article: 2005-09-3778v1 107/10/4090    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Tam, W. Articles by Knowles, D. M Search for Related Content PubMed PubMed Citation Articles by Tam, W. Articles by Knowles, D. M Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 20, 2005 Accepted January 7, 2006 Mutational analysis of PRDM1 indicates a tumor suppressor role in diffuse large B-cell lymphomas Wayne Tam*, Mario Gomez, Amy Chadburn, Joong W Lee, Wing C Chan, and Daniel M Knowles Department of Pathology and Laboratory Medicine, Joan & Sanford I. Weill Medical College of Cornell University, New York, NY, USA Department of Pathology, University of Nebraska Medical Center, Omaha, Nebraska, USA * Corresponding author; email: wtam{at}med.cornell.edu. 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 two of these cases, point mutations appear to be caused by RNA editing with G-to-A and U-to-G conversions. Other mutations include frameshift 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Oncogenic pathways in distinct DLBCL subgroups Hans Konrad Müller-Hermelink and Thomas Rüdiger Blood 2006 107: 3818. [Full Text] [PDF] This article has been cited by other articles: S. Desai, S. C. E. Bolick, M. Maurin, and K. L. Wright PU.1 Regulates Positive Regulatory Domain I-Binding Factor 1/Blimp-1 Transcription in Lymphoma Cells J. Immunol., November 1, 2009; 183(9): 5778 - 5787. [Abstract] [Full Text] [PDF] K. D'Costa, D. Emslie, D. Metcalf, G. K. Smyth, A. Karnowski, A. Kallies, S. L. Nutt, and L. M. Corcoran Blimp1 is limiting for transformation in a mouse plasmacytoma model Blood, June 4, 2009; 113(23): 5911 - 5919. [Abstract] [Full Text] [PDF] F. Asimakopoulos and H. E. Varmus Cell-Specific Transduction of Prdm1-Expressing Lineages Mediated by a Receptor for Avian Leukosis Virus Subgroup B J. Virol., May 15, 2009; 83(10): 4835 - 4843. 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