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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.

Publication ,  Journal Article
Young, KH; Weisenburger, DD; Dave, BJ; Smith, L; Sanger, W; Iqbal, J; Campo, E; Delabie, J; Gascoyne, RD; Ott, G; Rimsza, L; Jaffe, ES ...
Published in: Blood
December 15, 2007

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.

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Published In

Blood

DOI

ISSN

0006-4971

Publication Date

December 15, 2007

Volume

110

Issue

13

Start / End Page

4396 / 4405

Location

United States

Related Subject Headings

  • Tumor Suppressor Protein p53
  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • Prognosis
  • Mutation
  • Lymphoma, Large B-Cell, Diffuse
  • Immunology
  • Humans
  • Gene Expression Regulation, Neoplastic
  • Codon
  • Binding Sites
 

Citation

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Chicago
ICMJE
MLA
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Young, K. H., Weisenburger, D. D., Dave, B. J., Smith, L., Sanger, W., Iqbal, J., … Greiner, T. C. (2007). 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. Blood, 110(13), 4396–4405. https://doi.org/10.1182/blood-2007-02-072082
Young, Ken H., Dennis D. Weisenburger, Bhavana J. Dave, Lynette Smith, Warren Sanger, Javeed Iqbal, Elias Campo, et al. “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.Blood 110, no. 13 (December 15, 2007): 4396–4405. https://doi.org/10.1182/blood-2007-02-072082.
Young, Ken H., et al. “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.Blood, vol. 110, no. 13, Dec. 2007, pp. 4396–405. Pubmed, doi:10.1182/blood-2007-02-072082.
Young KH, Weisenburger DD, Dave BJ, Smith L, Sanger W, Iqbal J, Campo E, Delabie J, Gascoyne RD, Ott G, Rimsza L, Müller-Hermelink HK, Jaffe ES, Rosenwald A, Staudt LM, Chan WC, Greiner TC. 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. Blood. 2007 Dec 15;110(13):4396–4405.

Published In

Blood

DOI

ISSN

0006-4971

Publication Date

December 15, 2007

Volume

110

Issue

13

Start / End Page

4396 / 4405

Location

United States

Related Subject Headings

  • Tumor Suppressor Protein p53
  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • Prognosis
  • Mutation
  • Lymphoma, Large B-Cell, Diffuse
  • Immunology
  • Humans
  • Gene Expression Regulation, Neoplastic
  • Codon
  • Binding Sites