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dc.contributor.authorYoung, Ken H.
dc.contributor.authorLeroy, Karen
dc.contributor.authorMoller, Michael B.
dc.contributor.authorColleoni, Gisele Wally Braga [UNIFESP]
dc.contributor.authorSanchez-Beato, Margarita
dc.contributor.authorKerbauy, Fábio Rodrigues [UNIFESP]
dc.contributor.authorHaioun, Corinne
dc.contributor.authorEickhoff, Jens C.
dc.contributor.authorYoung, Allen H.
dc.contributor.authorGaulard, Philippe
dc.contributor.authorPiris, Miguel A.
dc.contributor.authorOberley, Terry D.
dc.contributor.authorRehrauer, William M.
dc.contributor.authorKahl, Brad S.
dc.contributor.authorMalter, James S.
dc.contributor.authorCampo, Elias
dc.contributor.authorDelabie, Jan
dc.contributor.authorGascoyne, Randy D.
dc.contributor.authorRosenwald, Andreas
dc.contributor.authorRimsza, Lisa
dc.contributor.authorHuang, James
dc.contributor.authorBraziel, Rita M.
dc.contributor.authorJaffe, Elaine S.
dc.contributor.authorWilson, Wyndham H.
dc.contributor.authorStaudt, Louis M.
dc.contributor.authorVose, Julie M.
dc.contributor.authorChan, Wing C.
dc.contributor.authorWeisenburger, Dennis D.
dc.contributor.authorGreiner, Timothy C.
dc.identifier.citationBlood. Washington: Amer Soc Hematology, v. 112, n. 8, p. 3088-3098, 2008.
dc.description.abstractThe purpose of this study is to correlate the presence of TP53 gene mutations with the clinical outcome of a cohort of patients with diffuse large B-cell lymphoma (DLBCL) assembled from 12 medical centers. TP53 mutations were identified in 102 of 477 patients, and the overall survival (OS) of patients with TP53 mutations was significantly worse than those with wild-type TP53 (P < .001). However, subsets of TP53 mutations were found to have different effects on OS. Mutations in the TP53 DNA-binding domains were the strongest predictors of poor OS (P < .001). Mutations in the Loop-Sheet-Helix and Loop-L3 were associated with significantly decreased OS (P = .002), but OS was not significantly affected by mutations in Loop-L2. A subset of missense mutations (His158, His175, Ser245, Gln248, His273, Arg280, and Arg282) in the DNA-binding domains had the worst prognosis. Multivariate analysis confirmed that the International Prognostic Index and mutations in the DNA-binding domains were independent predictors of OS. TP53 mutations also stratified patients with germinal center B cell-like DLBCL, but not nongerminal center B cell-like DLBCL, into molecularly distinct subsets with different survivals. This study shows the prognostic importance of mutations in the TP53 DNA-binding domains in patients with DLBCL.en
dc.description.sponsorshipUS Public Health Service
dc.description.sponsorshipNational Cancer Institute
dc.description.sponsorshipDepartment of Health and Human Services
dc.description.sponsorshipGundersen Medical Foundation
dc.description.sponsorshipUniversity of Wisconsin Paul P. Carbone Comprehensive Cancer Center
dc.description.sponsorshipLymphoma Research Foundation
dc.publisherAmer Soc Hematology
dc.rightsAcesso aberto
dc.titleStructural profiles of TP53 gene mutations predict clinical outcome in diffuse large B-cell lymphoma: an international collaborative studyen
dc.contributor.institutionUniv Wisconsin
dc.contributor.institutionUniv Paris 12
dc.contributor.institutionOdense Univ Hosp
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionSpanish Natl Canc Ctr CNIO
dc.contributor.institutionUniv Barcelona
dc.contributor.institutionNorwegian Radium Hosp
dc.contributor.institutionBritish Columbia Canc Agcy
dc.contributor.institutionUniv Wurzburg
dc.contributor.institutionUniv Arizona
dc.contributor.institutionOregon Hlth & Sci Univ
dc.contributor.institutionUniv Nebraska Med Ctr
dc.description.affiliationUniv Wisconsin, Sch Med & Publ Hlth, Paul P Carbone Comprehens Canc Ctr, Dept Pathol & Lab Med, Madison, WI 53792 USA
dc.description.affiliationUniv Wisconsin, Sch Med & Publ Hlth, Paul P Carbone Comprehens Canc Ctr, Dept Biostat & Med Informat, Madison, WI 53792 USA
dc.description.affiliationUniv Wisconsin, Sch Med & Publ Hlth, Paul P Carbone Comprehens Canc Ctr, Dept Hematol & Oncol, Madison, WI 53792 USA
dc.description.affiliationUniv Paris 12, Hop Henri Mondor, F-94010 Creteil, France
dc.description.affiliationOdense Univ Hosp, DK-5000 Odense, Denmark
dc.description.affiliationUniversidade Federal de São Paulo, São Paulo, Brazil
dc.description.affiliationSpanish Natl Canc Ctr CNIO, Madrid, Spain
dc.description.affiliationUniv Barcelona, Barcelona, Spain
dc.description.affiliationNorwegian Radium Hosp, Oslo, Norway
dc.description.affiliationBritish Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada
dc.description.affiliationUniv Wurzburg, Wurzburg, Germany
dc.description.affiliationUniv Arizona, Tucson, AZ USA
dc.description.affiliationOregon Hlth & Sci Univ, Portland, OR 97201 USA
dc.description.affiliationNCI, Bethesda, MD 20892 USA
dc.description.affiliationUniv Nebraska Med Ctr, Omaha, NE USA
dc.description.affiliationUnifespUniversidade Federal de São Paulo, São Paulo, Brazil
dc.description.sponsorshipIDUS Public Health Service: CA36727
dc.description.sponsorshipIDUS Public Health Service: CA84967
dc.description.sourceWeb of Science
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