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Title: Structural profiles of TP53 gene mutations predict clinical outcome in diffuse large B-cell lymphoma: an international collaborative study
Authors: Young, Ken H.
Leroy, Karen
Moller, Michael B.
Colleoni, Gisele Wally Braga [UNIFESP]
Sanchez-Beato, Margarita
Kerbauy, Fábio Rodrigues [UNIFESP]
Haioun, Corinne
Eickhoff, Jens C.
Young, Allen H.
Gaulard, Philippe
Piris, Miguel A.
Oberley, Terry D.
Rehrauer, William M.
Kahl, Brad S.
Malter, James S.
Campo, Elias
Delabie, Jan
Gascoyne, Randy D.
Rosenwald, Andreas
Rimsza, Lisa
Huang, James
Braziel, Rita M.
Jaffe, Elaine S.
Wilson, Wyndham H.
Staudt, Louis M.
Vose, Julie M.
Chan, Wing C.
Weisenburger, Dennis D.
Greiner, Timothy C.
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
Issue Date: 15-Oct-2008
Publisher: Amer Soc Hematology
Citation: Blood. Washington: Amer Soc Hematology, v. 112, n. 8, p. 3088-3098, 2008.
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.
ISSN: 0006-4971
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