SEARCH:   Advanced

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 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 Citation Map 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 Neoplasia Oncogenes and Tumor Suppressors Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA 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 From the Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York, NY; and the Department of Pathology, University of Nebraska Medical Center, Omaha, NE. 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. 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: 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. [Abstract] [Full Text] [PDF] A. L. Shaffer, N.C. T. Emre, P. B. Romesser, and L. M. Staudt IRF4: Immunity. Malignancy! Therapy? Clin. Cancer Res., May 1, 2009; 15(9): 2954 - 2961. [Abstract] [Full Text] [PDF] K. Nie, M. Gomez, P. Landgraf, J.-F. Garcia, Y. Liu, L. H.C. Tan, A. Chadburn, T. Tuschl, D. M. Knowles, and W. Tam MicroRNA-Mediated Down-Regulation of PRDM1/Blimp-1 in Hodgkin/Reed-Sternberg Cells: A Potential Pathogenetic Lesion in Hodgkin Lymphomas Am. J. Pathol., July 1, 2008; 173(1): 242 - 252. [Abstract] [Full Text] [PDF] S. Lugthart, E. van Drunen, Y. van Norden, A. van Hoven, C. A. J. Erpelinck, P. J. M. Valk, H. B. Beverloo, B. Lowenberg, and R. Delwel High EVI1 levels predict adverse outcome in acute myeloid leukemia: prevalence of EVI1 overexpression and chromosome 3q26 abnormalities underestimated Blood, April 15, 2008; 111(8): 4329 - 4337. [Abstract] [Full Text] [PDF] L. T. Lam, G. Wright, R. E. Davis, G. Lenz, P. Farinha, L. Dang, J. W. Chan, A. Rosenwald, R. D. Gascoyne, and L. M. Staudt Cooperative signaling through the signal transducer and activator of transcription 3 and nuclear factor-{kappa}B pathways in subtypes of diffuse large B-cell lymphoma Blood, April 1, 2008; 111(7): 3701 - 3713. [Abstract] [Full Text] [PDF] W. Tam, M. Gomez, and K. Nie Significance of PRDM1{beta} expression as a prognostic marker in diffuse large B-cell lymphomas Blood, February 15, 2008; 111(4): 2488 - 2489. [Full Text] [PDF] W.-L. Zhao, A. Janin, and S.-J. Chen Response: Multiple role of PRDM1{beta} involvement in diffuse large B-cell lymphoma Blood, February 15, 2008; 111(4): 2489 - 2490. [Full Text] [PDF] B. B. Ding, J. J. Yu, R. Y.-L. Yu, L. M. Mendez, R. Shaknovich, Y. Zhang, G. Cattoretti, and B. H. Ye Constitutively activated STAT3 promotes cell proliferation and survival in the activated B-cell subtype of diffuse large B-cell lymphomas Blood, February 1, 2008; 111(3): 1515 - 1523. [Abstract] [Full Text] [PDF] F. Mora-Lopez, E. Reales, J. A. Brieva, and A. Campos-Caro Human BSAP and BLIMP1 conform an autoregulatory feedback loop Blood, November 1, 2007; 110(9): 3150 - 3157. [Abstract] [Full Text] [PDF] C. W. Ross, P. D. Ouillette, C. M. Saddler, K. A. Shedden, and S. N. Malek Comprehensive Analysis of Copy Number and Allele Status Identifies Multiple Chromosome Defects Underlying Follicular Lymphoma Pathogenesis Clin. Cancer Res., August 15, 2007; 13(16): 4777 - 4785. [Abstract] [Full Text] [PDF] Y.-Y. Liu, C. Leboeuf, J.-Y. Shi, J.-M. Li, L. Wang, Y. Shen, J.-F. Garcia, Z.-X. Shen, Z. Chen, A. Janin, et al. Rituximab plus CHOP (R-CHOP) overcomes PRDM1-associated resistance to chemotherapy in patients with diffuse large B-cell lymphoma Blood, July 1, 2007; 110(1): 339 - 344. [Abstract] [Full Text] [PDF] A. Miremadi, M. Z. Oestergaard, P. D.P. Pharoah, and C. Caldas Cancer genetics of epigenetic genes Hum. Mol. Genet., April 15, 2007; 16(R1): R28 - R49. [Abstract] [Full Text] [PDF] G. Lenz, I. Nagel, R. Siebert, A. V. Roschke, W. Sanger, G. W. Wright, S. S. Dave, B. Tan, H. Zhao, A. Rosenwald, et al. Aberrant immunoglobulin class switch recombination and switch translocations in activated B cell-like diffuse large B cell lymphoma J. Exp. Med., March 19, 2007; 204(3): 633 - 643. [Abstract] [Full Text] [PDF] K. Nie, M. F. Gomez, P. Landgraf, J.-F. Garcia, Y. Liu, L. H.C. Tan, A. Chadburn, T. Tuschl, D. M. Knowles, and W. Tam MicroRNA-Mediated Translation Repression of PRDM1 in Hodgkin/Reed-Sternberg Cells - A Potential Pathogenetic Lesion in Hodgkin Lymphoma. Blood (ASH Annual Meeting Abstracts), November 16, 2006; 108(11): 614 - 614. [Abstract] [PDF] G. Cattoretti, R. Shaknovich, P. M. Smith, H.-M. Jack, V. V. Murty, and B. Alobeid Stages of Germinal Center Transit Are Defined by B Cell Transcription Factor Coexpression and Relative Abundance J. Immunol., November 15, 2006; 177(10): 6930 - 6939. [Abstract] [Full Text] [PDF]

	Copyright © 2006 by American Society of Hematology         Online ISSN: 1528-0020