TY - JOUR
T1 - Structural profiles of TP53 gene mutations predict clinical outcome in diffuse large B-cell lymphoma
T2 - An international collaborative study
AU - Young, Ken H.
AU - Leroy, Karen
AU - Møller, Michael B.
AU - Colleoni, Gisele W.B.
AU - Sánchez-Beato, Margarita
AU - Kerbauy, Fábio R.
AU - Haioun, Corinne
AU - Eickhoff, Jens C.
AU - Young, Allen H.
AU - Gaulard, Philippe
AU - Piris, Miguel A.
AU - Oberley, Terry D.
AU - Rehrauer, William M.
AU - Kahl, Brad S.
AU - Malter, James S.
AU - Campo, Elias
AU - Delabie, Jan
AU - Gascoyne, Randy D.
AU - Rosenwald, Andreas
AU - Rimsza, Lisa
AU - Huang, James
AU - Braziel, Rita M.
AU - Jaffe, Elaine S.
AU - Wilson, Wyndham H.
AU - Staudt, Louis M.
AU - Vose, Julie M.
AU - Chan, Wing C.
AU - Weisenburger, Dennis D.
AU - Greiner, Timothy C.
PY - 2008/10/15
Y1 - 2008/10/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=54049126176&partnerID=8YFLogxK
U2 - 10.1182/blood-2008-01-129783
DO - 10.1182/blood-2008-01-129783
M3 - Article
C2 - 18559976
AN - SCOPUS:54049126176
SN - 0006-4971
VL - 112
SP - 3088
EP - 3098
JO - Blood
JF - Blood
IS - 8
ER -