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dc.creatorDuran-Ferrer, M. (Martí)-
dc.creatorClot, G. (Guillem)-
dc.creatorNadeu, F. (Ferran)-
dc.creatorBeekman, R. (Renée)-
dc.creatorBaumann, T. (Tycho)-
dc.creatorNordlund, J. (Jessica)-
dc.creatorMarincevic-Zuniga, Y. (Yanara)-
dc.creatorLonnerholm, G. (Gudmar)-
dc.creatorRivas-Delgado, A. (Alfredo)-
dc.creatorMartín, S. (Silvia)-
dc.creatorRaquel-
dc.creatorCastellano, G. (Giancarlo)-
dc.creatorKulis, M. (Marta)-
dc.creatorQueirós, A. (Ana)-
dc.creatorSeung-Tae, L. (Lee)-
dc.creatorWiemels, J. (Joseph)-
dc.creatorRoyo, R. (Romina)-
dc.creatorPuiggros, M. (Montserrat)-
dc.creatorLu, J. (Junyan)-
dc.creatorGiné, E. (Eva)-
dc.creatorBea, S. (Silvia)-
dc.creatorJares, P. (Pedro)-
dc.creatorAgirre-Ena, X. (Xabier)-
dc.creatorProsper-Cardoso, F. (Felipe)-
dc.creatorLópez-Otín, C. (Carlos)-
dc.creatorPuente, X.S. (Xosé S.)-
dc.creatorOakes, C.C. (Christopher C.)-
dc.creatorZenz, T. (Thorsten)-
dc.creatorDelgado, J. (Julio)-
dc.creatorLópez-Guillermo, A. (Armando)-
dc.creatorCampo, E. (Elías)-
dc.creatorMartin-Subero, J.I. (Jose Ignacio)-
dc.date.accessioned2021-09-14T07:22:45Z-
dc.date.available2021-09-14T07:22:45Z-
dc.date.issued2020-
dc.identifier.citationDuran-Ferrer, M.; Clot, G.; Nadeu, F.; et al. "The proliferative history shapes the DNA methylome of B-cell tumors and predicts clinical outcome". Nature Cancer. 1 (11), 2020, 1066 - 1081es
dc.identifier.issn2662-1347-
dc.identifier.urihttps://hdl.handle.net/10171/61991-
dc.description.abstractWe report a systematic analysis of the DNA methylation variability in 1,595 samples of normal cell subpopulations and 14 tumor subtypes spanning the entire human B-cell lineage. Differential methylation among tumor entities relates to differences in cellular origin and to de novo epigenetic alterations, which allowed us to build an accurate machine learning-based diagnostic algorithm. We identify extensive individual-specific methylation variability in silenced chromatin associated with the proliferative history of normal and neoplastic B cells. Mitotic activity generally leaves both hyper- and hypomethylation imprints, but some B-cell neoplasms preferentially gain or lose DNA methylation. We construct a DNA-methylation-based mitotic clock, called epiCMIT, whose lapse magnitude represents a strong independent prognostic variable in B-cell tumors and is associated with particular driver genetic alterations. Our findings reveal DNA methylation as a holistic tracer of B-cell tumor developmental history, with implications in differential diagnosis and the prediction of clinical outcome. Martin-Subero and colleagues analyze DNA methylation patterns in B-cell tumors and their normal cells of origin, and develop epiCMIT, a methylation-based mitotic clock with prognostic relevance.-
dc.description.sponsorshipThis research was funded by the European Union’s Seventh Framework Programme through the Blueprint Consortium (grant agreement 282510), the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (Project BCLLATLAS, grant agreement 810287), Generalitat de Catalunya Suport Grups de Recerca AGAUR 2017-SGR-1142 (to E.C.) and 2017-SGR-736 (to J.I.M.-S.), Ministerio de Ciencia, Innovación y Universidades of the Spanish Government (MCIU), Grants RTI2018-094274-B-I00 (to E.C.) and SAF2017-86126-R (to J.I.M.-S.) as well as Proyecto Medicina Personalizada PERMED (Grant PMP15/00007), which is part of Plan Nacional de I+D+I and is co-financed by the ISCIII-Sub-Directorate General for Evaluation and the European Regional Development Fund (FEDER-“Una manera de Hacer Europa”), CIBERONC (CB16/12/00225, CB16/12/00334, CB16/12/00236, and CB16/12/00489), the Accelerator award CRUK/AIRC/ AECC joint funder-partnership, research funding from Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III PI17/01061 (SB), Ministerio de Ciencia, Innovación y Universidades (MCIU), RTI2018-094274-B-I00, SAF2015-64885-R (EC), the NIH grant number 1 P01CA229100 (EC), and the European Regional Development Fund “Una manera de fer Europa”, CERCA Programme/Generalitat de Catalunya. FN is supported by a pre- doctoral fellowship of the Ministerio de Economía y Competitividad (MINECO, BES-2016-076372). E.C. is an Academia Researcher of the “Institució Catalana de Recerca i Estudis Avançats” (ICREA) of the Generalitat de Catalunya. This work was partially developed at the Centro Esther Koplowitz (CEK, Barcelona, Spain).-
dc.language.isoen-
dc.relationinfo:eu-repo/grantAgreement/EC/FP7/282510/EU-
dc.relationBCLLATLAS, grant agreement 810287-
dc.rightsinfo:eu-repo/semantics/openAccess-
dc.subjectChronic lymphocytic-leukemia-
dc.subjectMultiple-myeloma-
dc.subjectMolecular classification-
dc.subjectMethylation landscape-
dc.subjectLymphoma-
dc.subjectExpression-
dc.subjectGenes-
dc.subjectHypermethylation-
dc.subjectDifferentiation-
dc.subjectHypomethylation-
dc.titleThe proliferative history shapes the DNA methylome of B-cell tumors and predicts clinical outcome-
dc.typeinfo:eu-repo/semantics/article-
dc.identifier.doi10.1038/s43018-020-00131-2-
dadun.citation.endingPage1081-
dadun.citation.number11-
dadun.citation.publicationNameNature Cancer-
dadun.citation.startingPage1066-
dadun.citation.volume1-

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