@article{3c489099f74745acbe98a59edb6dd182,
title = "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",
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 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.",
author = "Yong Li and Gordon, {Michael W.} and Xu-Monette, {Zijun Y.} and Carlo Visco and Alexander Tzankov and Dehui Zou and Lugui Qiu and Santiago Montes-Moreno and Karen Dybkaer and Attilio Orazi and Youli Zu and Govind Bhagat and Richards, {Kristy L.} and Hsi, {Eric D.} and Choi, {William W.L.} and {Van Krieken}, {J. Han} and Qin Huang and Weiyun Ai and Maurilio Ponzoni and Ferreri, {Andr{\'e}s J.M.} and Winter, {Jane N.} and Go, {Ronald S.} and Piris, {Miguel A.} and M{\o}ller, {Michael B.} and Lin Wu and Michael Wang and Ramos, {Kenneth S.} and Medeiros, {L. Jeffrey} and Young, {Ken H.}",
note = "Funding Information: Contribution: Y.L., K.H.Y., Z.Y.X.-M., and M.W.G. designed and conducted the research, performed and supported the statistical analysis, and wrote the manuscript; Y.L., Z.Y.X.-M., L.W., C.V., A.T., D.Z., L.Q., S.M.-M., K.D., A.C., Y.Z., G.B., K.L.R., E.D.H., W.W.L.C., J.H.v.K., Q.H., W.A., M.P., A.J.M.F., J.N.W., R.S.G., M.A.P., M.B.M., L.W., M.W., K.S.R., L.J.M., and K.H.Y. contributed vital new reagents, resources, and analytical tools under approval by the institutional review boards and the material transfer agreement; Z.Y.X.-M., C.V., A.T., S.M.-M., K.D., A.O., Y.Z., G.B., K.L.R., E.D.H., W.W.L.C., J.H.v.K., Q.H., W.A., M.P., A.J.M.F., J.N.W., R.S.G., M.A.P., M.B.M., M.W., L.J.M., and K.H.Y. collected clinical and follow-up data under approval by the institutional review boards and the material transfer agreement; Y.L., Z.Y.X.-M., C.V., and K.H.Y. analyzed the data and performed the statistical analysis; and all authors contributed vital strategies, participated in discussions, and provided scientific input. Funding Information: 1Department of Biochemistry and Molecular Biology, University of Louisville School of Medicine, Brown Cancer Center, Louisville, KY; 2Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX; 3Department of Hematology, San Bortolo Hospital, Vicenza, Italy; 4Department of Pathology, University Hospital, Basel, Switzerland; 5Institute of Hematology, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, China; 6Department of Pathology, Hospital Universitario Marqu{\'e}s de Valdecilla/IFIMAV, Santander, Spain; 7Department of Hematology, Aarhus University Hospital, Aalborg, Denmark; 8Department of Pathology, Weill Medical College of Cornell University, New York, NY; 9Department of Pathology, The Methodist Hospital, Houston, TX; 10Department of Pathology, Columbia University School of Medicine, New York, NY; 11Department of Hematology, University of North Carolina School of Medicine, Chapel Hill, NC; 12Department of Pathology, Cleveland Clinic, Cleveland, OH; 13Department of Pathology, University of Hong Kong Li Ka Shing Faculty of Medicine, Hong Kong, China; 14Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands; 15Department of Pathology, City of Hope National Medical Center, Duarte, CA; 16Department of Hematology, University of California San Francisco School of Medicine, San Francisco, CA; 17Departments of Hematology and Pathology, San Raffaele H. Scientific Institute, Milan, Italy; 18Department of Hematology, Feinberg School of Medicine, Northwestern University, Chicago, IL; 19Department of Hematology, Gundersen Lutheran Health System, La Crosse, WI; 20Department of Pathology, Odense University Hospital, Odense, Denmark; 21Department of Genomic Oncology, Roche Molecular Systems Inc., Pleasanton, CA; and 22Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX Funding Information: This work was supported by grants from the National Cancer Institute/National Institutes of Health (R01CA138688, 1RC1CA146299, P50CA136411, and P50CA142509 to Y.L. and K.H.Y.); the Shannon Timmins Leukemia Fellowship Award at The University of Texas MD Anderson Cancer Center (Z.Y.X.-M.); and The University of Texas MD Anderson Cancer Center Institutional Research and Development Fund, Institutional Research Grant Award, an MD Anderson Cancer Center Lymphoma Specialized Programs of Research Excellence Research Development Program Award, an MD Anderson Cancer Center Myeloma Specialized Programs of Research Excellence Research Development Program Award, a Gundersen Lutheran Medical Foundation Award, MD Anderson Cancer Center Collaborative Funds with Roche Molecular System, HTG Molecular Diagnostics, and Daiichi Sankyo Pharmaceutical (K.H.Y.). Publisher Copyright: {\textcopyright} 2013 by The American Society of Hematology.",
year = "2013",
month = may,
day = "30",
doi = "10.1182/blood-2012-12-471722",
language = "English (US)",
volume = "121",
pages = "4529--4540",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "22",
}