Structural profiles of TP53 gene mutations predict clinical outcome in diffuse large B-cell lymphoma: an international collaborative study

Structural profiles of TP53 gene mutations predict clinical outcome in diffuse large B-cell lymphoma: an international collaborative study

Author Young, Ken H. Google Scholar
Leroy, Karen Google Scholar
Moller, Michael B. Google Scholar
Colleoni, Gisele Wally Braga Autor UNIFESP Google Scholar
Sanchez-Beato, Margarita Google Scholar
Kerbauy, Fábio Rodrigues Autor UNIFESP Google Scholar
Haioun, Corinne Google Scholar
Eickhoff, Jens C. Google Scholar
Young, Allen H. Google Scholar
Gaulard, Philippe Google Scholar
Piris, Miguel A. Google Scholar
Oberley, Terry D. Google Scholar
Rehrauer, William M. Google Scholar
Kahl, Brad S. Google Scholar
Malter, James S. Google Scholar
Campo, Elias Google Scholar
Delabie, Jan Google Scholar
Gascoyne, Randy D. Google Scholar
Rosenwald, Andreas Google Scholar
Rimsza, Lisa Google Scholar
Huang, James Google Scholar
Braziel, Rita M. Google Scholar
Jaffe, Elaine S. Google Scholar
Wilson, Wyndham H. Google Scholar
Staudt, Louis M. Google Scholar
Vose, Julie M. Google Scholar
Chan, Wing C. Google Scholar
Weisenburger, Dennis D. Google Scholar
Greiner, Timothy C. Google Scholar
Institution Univ Wisconsin
Univ Paris 12
Odense Univ Hosp
Universidade Federal de São Paulo (UNIFESP)
Spanish Natl Canc Ctr CNIO
Univ Barcelona
Norwegian Radium Hosp
British Columbia Canc Agcy
Univ Wurzburg
Univ Arizona
Oregon Hlth & Sci Univ
Univ Nebraska Med Ctr
Abstract 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.
Language English
Sponsor US Public Health Service
National Cancer Institute
Department of Health and Human Services
Gundersen Medical Foundation
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
Lymphoma Research Foundation
Grant number US Public Health Service: CA36727
US Public Health Service: CA84967
Date 2008-10-15
Published in Blood. Washington: Amer Soc Hematology, v. 112, n. 8, p. 3088-3098, 2008.
ISSN 0006-4971 (Sherpa/Romeo, impact factor)
Publisher Amer Soc Hematology
Extent 3088-3098
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000259866100021

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