Single nucleotide variation in the TP53 3′ untranslated region in diffuse large B-cell lymphoma treated with rituximab-CHOP: A report from the International DLBCL Rituximab-CHOP Consortium Program

Yong Li, Michael W. Gordon, Zijun Y. Xu-Monette, Carlo Visco, Alexander Tzankov, Dehui Zou, Lugui Qiu, Santiago Montes-Moreno, Karen Dybkaer, Attilio Orazi, Youli Zu, Govind Bhagat, Kristy L. Richards, Eric D. Hsi, William W.L. Choi, J. Han Van Krieken, Qin Huang, Weiyun Ai, Maurilio Ponzoni, Andrés J.M. FerreriJane N. Winter, Ronald S. Go, Miguel A. Piris, Michael B. Møller, Lin Wu, Michael Wang, Kenneth S. Ramos, L. Jeffrey Medeiros, Ken H. Young

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

We identified multiple single nucleotide variants (SNVs) in the TP53 3′ untranslated region (3′UTR) in tumor specimens from 244 patients with diffuse large B-cell lymphoma (DLBCL). Patients carrying a wild-type TP53 coding sequence (CDS) and 1 or more 3′UTR SNVs had a better 5-year survival rate than patients carrying a wild-type CDS and the reference 3′UTR, yet there is no statistically significance difference in overall survival (OS). In contrast, 3′UTR variation predicted poorer OS for patients with a mutant TP53 CDS.We then sequenced TP53 3′UTR in 247 additional DLBCL patients as a validation set. Altogether, we identified 187 novel SNVs; 36 occurred at least twice. Most of the newly identified 3′UTR SNVs were located at sites that are complementary to seed sequences of microRNAs (miRNAs) that are predicted or experimentally known to target TP53. Three SNVs disrupt the seedmatch betweenmiR-125b and the TP53 3′UTR, thereby impeding suppression of p53 by this miRNA. In addition, a germline SNV (rs78378222) located in the TP53 polyadenylation signal resulted in downregulation of both p53 messenger RNA and protein levels and reduction of cellular apoptosis. This study is the first to demonstrate the prognostic value of the TP53 3′UTR in cancer.

Original languageEnglish (US)
Pages (from-to)4529-4540
Number of pages12
JournalBlood
Volume121
Issue number22
DOIs
StatePublished - May 30 2013

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Fingerprint Dive into the research topics of 'Single nucleotide variation in the TP53 3′ untranslated region in diffuse large B-cell lymphoma treated with rituximab-CHOP: A report from the International DLBCL Rituximab-CHOP Consortium Program'. Together they form a unique fingerprint.

  • Cite this

    Li, Y., Gordon, M. W., Xu-Monette, Z. Y., Visco, C., Tzankov, A., Zou, D., Qiu, L., Montes-Moreno, S., Dybkaer, K., Orazi, A., Zu, Y., Bhagat, G., Richards, K. L., Hsi, E. D., Choi, W. W. L., Van Krieken, J. H., Huang, Q., Ai, W., Ponzoni, M., ... Young, K. H. (2013). Single nucleotide variation in the TP53 3′ untranslated region in diffuse large B-cell lymphoma treated with rituximab-CHOP: A report from the International DLBCL Rituximab-CHOP Consortium Program. Blood, 121(22), 4529-4540. https://doi.org/10.1182/blood-2012-12-471722