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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 (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 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 Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 15, 2008 Accepted June 2, 2008 Structural profiles of TP53 gene mutations predict clinical outcome in diffuse large B-cell lymphoma: an international collaborative study Ken H Young*, Karen Leroy, Michael B Moller, Gisele WB Colleoni, Margarita Sanchez-Beato, Fabio R Kerbauy, Corinne Haioun, Jens C Eickhoff, Allen H Young, Philippe Gaulard, Miguel A Piris, Terry D Oberley, William M Rehrauer, Brad S Kahl, James S Malter, Elias Campo, Jan Delabie, Randy D Gascoyne, Andreas Rosenwald, Lisa Rimsza, James Huang, Rita M Braziel, Elaine S Jaffe, Wyndham H Wilson, Louis M Staudt, Julie M Vose, Wing C Chan, Dennis D Weisenburger, and Timothy C Greiner Department of Pathology & Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States Hospital Henri Mondor, Paris, France Odense University Hospital, Odense, Denmark Federal University of Sao Paulo, Sao Paulo, Brazil Spanish National Cancer Center, CNIO, Madrid, Spain Federal University of Sao Paulo, Sao Paolo, Brazil University of Barcelona, Barcelona, Spain Norwegian Radium Hospital, Oslo, Norway British Columbia Cancer Agency, Vancover, BC, Canada University of Wuerzburg, Wuerzburg, Germany University of Arizona, Tucson, AZ, United States Oregon Health & Science University, Portland, OR, United States National Cancer Institute, National Institutes of Health, Bethesda, MD, United States University of Nebraska Medical Center, Omaha, NE, United States * Corresponding author; email: khyoung{at}wisc.edu. 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=0.0006). 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=0.0003). Mutations in the Loop-Sheet-Helix and Loop-L3 were associated with significantly decreased OS (p=0.002), 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 non-germinal center B-cell-like DLBCL, into molecularly-distinct subsets with different survivals. This study demonstrates 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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