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Blood, 15 December 2007, Vol. 110, No. 13, pp. 4396-4405. Prepublished online as a Blood First Edition Paper on October 25, 2007; DOI 10.1182/blood-2007-02-072082. This Article Full Text Full Text (PDF) Supplemental Tables All Versions of this Article: blood-2007-02-072082v1 blood-2007-02-072082v2 110/13/4396    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 Young, K. H. Articles by Greiner, T. C. Search for Related Content PubMed PubMed Citation Articles by Young, K. H. Articles by Greiner, T. C. Related Collections Gene Expression Immunobiology Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Mutations in the DNA-binding codons of TP53, which are associated with decreased expression of TRAILreceptor-2, predict for poor survival in diffuse large B-cell lymphoma Ken H. Young1, Dennis D. Weisenburger1, Bhavana J. Dave2, Lynette Smith3, Warren Sanger2, Javeed Iqbal1, Elias Campo4, Jan Delabie5, Randy D. Gascoyne6, German Ott7, Lisa Rimsza8, H. Konrad Müller-Hermelink7, Elaine S. Jaffe9, Andreas Rosenwald7, Louis M. Staudt10, Wing C. Chan1, and Timothy C. Greiner1 1 Department of Pathology and Microbiology, 2 Human Genetics Laboratory, Munroe Meyer Institute for Genetics and Rehabilitation, and 3 Department of Preventive and Societal Medicine, University of Nebraska Medical Center, Omaha; 4 University of Barcelona, Barcelona, Spain; 5 Norwegian Radium Hospital, Oslo, Norway; 6 British Columbia Cancer Agency, Vancouver, BC; 7 Institute of Pathology, University of Würzburg, Würzburg, Germany; 8 Department of Pathology, University of Arizona, Tucson; 9 Laboratory of Pathology and 10 Metabolism Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD Mutations of the TP53 tumor suppressor gene have been associated with poor survival in some series of diffuse large B-cell lymphoma (DLBCL) but not in other studies. The purpose of this study was to identify the frequency of TP53 alterations (mutations or deletions), characterize the gene expression of mutant/deleted cases, and determine the effects of mutations on survival. In a series of DLBCL that had previous gene expression profiling, we identified 24 mutations in 113 cases (21%). There was no difference in the frequency of mutations in the molecular subgroups of DLBCL. Twelve (50%) of the 24 cases had mutations localized to the DNA-binding codons in the core domain of TP53. The presence of any TP53 mutation correlated with poor overall survival (OS; P = .044), but DNA-binding mutations were the most significant predictor of poor OS (P < .001). Multivariate analysis confirmed that the International Prognostic Index, tumor size, and TP53 DNA-binding mutations were independent predictors of OS. Gene expression analysis showed that TRAILreceptor-2 (DR5) was the most differentially underexpressed gene in the TP53 mutated cases. Investigation is warranted into targeted therapy toward TRAIL receptor-2, to potentially bypass the adverse effect of mutated TP53 in DLBCL. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Bea and E. Campo Secondary genomic alterations in non-Hodgkin's lymphomas: tumor-specific profiles with impact on clinical behavior Haematologica, May 1, 2008; 93(5): 641 - 645. [Full Text] [PDF]

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