Details

Autor(en) / Beteiligte

• Young, Ken H.
• Weisenburger, Dennis D.
• Dave, Bhavana J.
• Smith, Lynette
• Sanger, Warren
• Iqbal, Javeed
• Campo, Elias
• Delabie, Jan
• Gascoyne, Randy D.
• Ott, German
• Rimsza, Lisa
• Müller-Hermelink, H. Konrad
• Jaffe, Elaine S.
• Rosenwald, Andreas
• Staudt, Louis M.
• Chan, Wing C.
• Greiner, Timothy C.

Titel

Mutations in the DNA-binding codons of TP53, which are associated with decreased expression of TRAILreceptor-2, predict for poor survival in diffuse large B-cell lymphoma

Ist Teil von

• Blood, 2007-12, Vol.110 (13), p.4396-4405

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2007

Quelle

MEDLINE

Beschreibungen/Notizen

• Mutations of the TP53 tumor suppressor gene have been associated with poor survival in some series of diffuse large B-cell lymphoma (DLBCL) but not in other studies. The purpose of this study was to identify the frequency of TP53 alterations (mutations or deletions), characterize the gene expression of mutant/deleted cases, and determine the effects of mutations on survival. In a series of DLBCL that had previous gene expression profiling, we identified 24 mutations in 113 cases (21%). There was no difference in the frequency of mutations in the molecular subgroups of DLBCL. Twelve (50%) of the 24 cases had mutations localized to the DNA-binding codons in the core domain of TP53. The presence of any TP53 mutation correlated with poor overall survival (OS; P = .044), but DNA-binding mutations were the most significant predictor of poor OS (P < .001). Multivariate analysis confirmed that the International Prognostic Index, tumor size, and TP53 DNA-binding mutations were independent predictors of OS. Gene expression analysis showed that TRAILreceptor-2 (DR5) was the most differentially underexpressed gene in the TP53 mutated cases. Investigation is warranted into targeted therapy toward TRAIL receptor-2, to potentially bypass the adverse effect of mutated TP53 in DLBCL.