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Blood, 15 October 2008, Vol. 112, No. 8, pp. 3088-3098. Prepublished online as a Blood First Edition Paper on June 17, 2008; DOI 10.1182/blood-2008-01-129783. This Article Full Text Full Text (PDF) Supplemental Appendix All Versions of this Article: blood-2008-01-129783v1 112/8/3088    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 Neoplasia Clinical Trials and Observations Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL TRIALS AND OBSERVATIONS Structural profiles of TP53 gene mutations predict clinical outcome in diffuse large B-cell lymphoma: an international collaborative study Ken H. Young13, Karen Leroy4, Michael B. Møller5, Gisele W. B. Colleoni6, Margarita Sánchez-Beato7, Fábio R. Kerbauy6, Corinne Haioun4, Jens C. Eickhoff13, Allen H. Young13, Philippe Gaulard4, Miguel A. Piris7, Terry D. Oberley13, William M. Rehrauer13, Brad S. Kahl13, James S. Malter13, Elias Campo8, Jan Delabie9, Randy D. Gascoyne10, Andreas Rosenwald11, Lisa Rimsza12, James Huang13, Rita M. Braziel13, Elaine S. Jaffe14, Wyndham H. Wilson14, Louis M. Staudt14, Julie M. Vose15, Wing C. Chan15, Dennis D. Weisenburger15, and Timothy C. Greiner15 Departments of1 Pathology and Laboratory Medicine, 2 Biostatistics & Medical Informatics, 3 Hematology & Oncology, University of Wisconsin School of Medicine and Public Health, University of of Wisconsin Paul P. Carbone Comprehensive Cancer Center, Madison; 4 Université Paris 12, Hôpital Henri Mondor, Créteil, France; 5 Odense University Hospital, Odense, Denmark; 6 Federal University of São Paulo, São Paulo, Brazil; 7 Spanish National Cancer Center (CNIO), Madrid, Spain; 8 University of Barcelona, Barcelona, Spain; 9 Norwegian Radium Hospital, Oslo, Norway; 10 British Columbia Cancer Agency, Vancouver, BC; 11 University of Würzburg, Würzburg, Germany; 12 University of Arizona, Tucson; 13 Oregon Health & Science University, Portland; 14 National Cancer Institute, Bethesda, MD; and 15 University of Nebraska Medical Center, Omaha The purpose of this study is to correlate the presence of TP53 gene mutations with the clinical outcome of a cohort of patients with diffuse large B-cell lymphoma (DLBCL) assembled from 12 medical centers. TP53 mutations were identified in 102 of 477 patients, and the overall survival (OS) of patients with TP53 mutations was significantly worse than those with wild-type TP53 (P < .001). However, subsets of TP53 mutations were found to have different effects on OS. Mutations in the TP53 DNA-binding domains were the strongest predictors of poor OS (P < .001). Mutations in the Loop-Sheet-Helix and Loop-L3 were associated with significantly decreased OS (P = .002), but OS was not significantly affected by mutations in Loop-L2. A subset of missense mutations (His158, His175, Ser245, Gln248, His273, Arg280, and Arg282) in the DNA-binding domains had the worst prognosis. Multivariate analysis confirmed that the International Prognostic Index and mutations in the DNA-binding domains were independent predictors of OS. TP53 mutations also stratified patients with germinal center B cell–like DLBCL, but not nongerminal center B cell–like DLBCL, into molecularly distinct subsets with different survivals. This study shows the prognostic importance of mutations in the TP53 DNA-binding domains in patients with DLBCL. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: P53 mutations in lymphomas: position matters Arnold J. Levine and Evan Vosburgh Blood 2008 112: 2997-2998. [Full Text] [PDF] This article has been cited by other articles: D. Dornan, F. Bennett, Y. Chen, M. Dennis, D. Eaton, K. Elkins, D. French, M. A. T. Go, A. Jack, J. R. Junutula, et al. Therapeutic potential of an anti-CD79b antibody-drug conjugate, anti-CD79b-vc-MMAE, for the treatment of non-Hodgkin lymphoma Blood, September 24, 2009; 114(13): 2721 - 2729. [Abstract] [Full Text] [PDF]

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