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
| Autor: | Lin Wu, Maurilio Ponzoni, Karen Dybkær, Youli Zu, J. Han van Krieken, Qin Huang, Eric D. Hsi, Weiyun Z. Ai, Govind Bhagat, Ronald S. Go, Dehui Zou, William W.L. Choi, Kristy L. Richards, Michael W. Gordon, Miguel A. Piris, L. Jeffrey Medeiros, Carlo Visco, Michael Boe Møller, Lugui Qiu, Attilio Orazi, Zijun Y. Xu-Monette, Yong Li, Kenneth S. Ramos, Alexander Tzankov, Ken H. Young, Santiago Montes-Moreno, Andrés J.M. Ferreri, Jane N. Winter, Michael Wang |
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| Přispěvatelé: | Li, Y, Gordon, Mw, Xu Monette, Zy, Visco, C, Tzankov, A, Zou, D, Qiu, L, Montes Moreno, S, Dybkaer, K, Orazi, A, Zu, Y, Bhagat, G, Richards, Kl, Hsi, Ed, Choi, Ww, van Krieken, Jh, Huang, Q, Ai, W, Ponzoni, Maurilio, Ferreri, Aj, Winter, Jn, Go, R, Piris, Ma, Møller, Mb, Wu, L, Wang, M, Ramos, K, Medeiros, Lj, Young, K. H. |
| Rok vydání: | 2013 |
| Předmět: |
Untranslated region
Lymphoma endocrine system diseases Kaplan-Meier Estimate CHOP Biochemistry Antibodies Monoclonal Murine-Derived immune system diseases hemic and lymphatic diseases Monoclonal Antineoplastic Combined Chemotherapy Protocols Coding region 3' Untranslated Regions Tumor Lymphoid Neoplasia Single Nucleotide Hematology Prognosis Translational research Tissue engineering and pathology [ONCOL 3] Diffuse Vincristine Rituximab Lymphoma Large B-Cell Diffuse medicine.drug Murine-Derived 5' Untranslated Regions Antineoplastic Agents Cell Line Tumor Cyclophosphamide Doxorubicin Genetic Testing Germ-Line Mutation Humans MicroRNAs Polymorphism Single Nucleotide Prednisone Retrospective Studies Tumor Suppressor Protein p53 Immunology Biology Antibodies Cell Line Germline mutation stomatognathic system Large B-Cell medicine Polymorphism neoplasms Three prime untranslated region Cell Biology medicine.disease Molecular biology Diffuse large B-cell lymphoma |
| Zdroj: | Blood, 121, 4529-40 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, Ferreri, A J M, Winter, J N, Go, R S, Piris, M A, Møller, M B, Wu, L, Wang, M, Ramos, K S, Medeiros, L J & 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, vol. 121, no. 22, pp. 4529-40 . https://doi.org/10.1182/blood-2012-12-471722 Li, Y, Gordon, M W, Xu-Monette, Z Y, Visco, C, Tzankov, A, Zou, D, Qiu, L, Montes-Moreno, S, Dybkær, 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, Ferreri, A J M, Winter, J N, Go, R S, Piris, M A, Møller, M B, Wu, L, Wang, M, Ramos, K S, Medeiros, L J & 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, vol. 121, no. 22, pp. 4529-40 . https://doi.org/10.1182/blood-2012-12-471722 Blood, 121, 22, pp. 4529-40 |
| ISSN: | 7837-8222 0006-4971 |
| DOI: | 10.1182/blood-2012-12-471722 |
| Popis: | Contains fulltext : 185425.pdf (Publisher’s version ) (Closed access) 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 seed match between miR-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. |
| Databáze: | OpenAIRE |
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