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The proliferative h...
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Duran-Ferrer, MartiInst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain.;CIBERONC, Ctr Invest Biomed Red Canc, Madrid, Spain.
(author)
The proliferative history shapes the DNA methylome of B-cell tumors and predicts clinical outcome
- Article/chapterEnglish2020
Publisher, publication year, extent ...
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2020-11-02
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Springer Nature,2020
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:uu-436028
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-436028URI
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https://doi.org/10.1038/s43018-020-00131-2DOI
Supplementary language notes
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Language:English
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Summary in:English
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Classification
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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We 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.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
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Clot, GuillemInst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain.;CIBERONC, Ctr Invest Biomed Red Canc, Madrid, Spain.
(author)
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Nadeu, FerranInst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain.;CIBERONC, Ctr Invest Biomed Red Canc, Madrid, Spain.
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Beekman, ReneeInst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain.;CIBERONC, Ctr Invest Biomed Red Canc, Madrid, Spain.
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Baumann, TychoCIBERONC, Ctr Invest Biomed Red Canc, Madrid, Spain.;IDIBAPS, Hosp Clin, Serv Hematol, Barcelona, Spain.
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Nordlund, JessicaUppsala universitet,Molekylär medicin,Science for Life Laboratory, SciLifeLab(Swepub:uu)jesno775
(author)
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Marincevic-Zuniga, YanaraUppsala universitet,Molekylär medicin,Science for Life Laboratory, SciLifeLab(Swepub:uu)yanma214
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Lönnerholm, Gudmar,1941-Uppsala universitet,Barnneurologi/Barnonkologi(Swepub:uu)gudmarlh
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Rivas-Delgado, AlfredoInst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain.;IDIBAPS, Hosp Clin, Serv Hematol, Barcelona, Spain.
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Martin, SilviaInst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain.;CIBERONC, Ctr Invest Biomed Red Canc, Madrid, Spain.
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Ordonez, RaquelCIBERONC, Ctr Invest Biomed Red Canc, Madrid, Spain.;IDISNA, Ctr Invest Med Aplicada CIMA, Pamplona, Spain.
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Castellano, GiancarloInst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain.
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Kulis, MartaInst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain.
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Queiros, Ana C.Inst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain.
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Lee, Seung-TaeYonsei Univ, Coll Med, Dept Lab Med, Seoul, South Korea.
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Wiemels, JosephUniv Southern Calif, Ctr Genet Epidemiol, Los Angeles, CA 90007 USA.
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Royo, RominaUniv Barcelona, Spanish Natl Bioinformat Inst, Inst Recerca Biomed IRB, Programa Conjunto Biol Computac,Barcelona Superco, Barcelona, Spain.
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Puiggros, MontserratUniv Barcelona, Spanish Natl Bioinformat Inst, Inst Recerca Biomed IRB, Programa Conjunto Biol Computac,Barcelona Superco, Barcelona, Spain.
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Lu, JunyanEuropean Mol Biol Lab EMBL, Heidelberg, Germany.
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Gine, EvaInst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain.;CIBERONC, Ctr Invest Biomed Red Canc, Madrid, Spain.;IDIBAPS, Hosp Clin, Serv Hematol, Barcelona, Spain.
(author)
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Bea, SilviaInst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain.;CIBERONC, Ctr Invest Biomed Red Canc, Madrid, Spain.;Ohio State Univ, Dept Internal Med, Div Hematol, Columbus, OH 43210 USA.
(author)
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Jares, PedroInst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain.;CIBERONC, Ctr Invest Biomed Red Canc, Madrid, Spain.;Ohio State Univ, Dept Internal Med, Div Hematol, Columbus, OH 43210 USA.
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Agirre, XabierCIBERONC, Ctr Invest Biomed Red Canc, Madrid, Spain.;IDISNA, Ctr Invest Med Aplicada CIMA, Pamplona, Spain.
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Prosper, FelipeCIBERONC, Ctr Invest Biomed Red Canc, Madrid, Spain.;IDISNA, Ctr Invest Med Aplicada CIMA, Pamplona, Spain.;Univ Navarra, Clin Univ Navarra, Hematol & Cell Therapy Dept, Pamplona, Spain.
(author)
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Lopez-Otin, CarlosCIBERONC, Ctr Invest Biomed Red Canc, Madrid, Spain.;Univ Oviedo, Inst Univ Oncol IUOPA, Dept Bioquim & Biol Mol, Oviedo, Spain.
(author)
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Puente, Xose S.CIBERONC, Ctr Invest Biomed Red Canc, Madrid, Spain.;Univ Oviedo, Inst Univ Oncol IUOPA, Dept Bioquim & Biol Mol, Oviedo, Spain.
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Oakes, Christopher C.Ohio State Univ, Dept Internal Med, Div Hematol, Columbus, OH 43210 USA.
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Zenz, ThorstenOhio State Univ, Dept Internal Med, Div Hematol, Columbus, OH 43210 USA.;Univ Hosp Zurich, Dept Med Oncol & Hematol, Zurich, Switzerland.;Univ Zurich, Zurich, Switzerland.
(author)
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Delgado, JulioInst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain.;CIBERONC, Ctr Invest Biomed Red Canc, Madrid, Spain.;IDIBAPS, Hosp Clin, Serv Hematol, Barcelona, Spain.
(author)
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Lopez-Guillermo, ArmandoInst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain.;CIBERONC, Ctr Invest Biomed Red Canc, Madrid, Spain.;IDIBAPS, Hosp Clin, Serv Hematol, Barcelona, Spain.
(author)
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Campo, EliasInst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain.;CIBERONC, Ctr Invest Biomed Red Canc, Madrid, Spain.;Univ Barcelona, Fac Med, Dept Fonaments Clin, Barcelona, Spain.
(author)
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Ignacio Martin-Subero, JoseInst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain.;CIBERONC, Ctr Invest Biomed Red Canc, Madrid, Spain.;Univ Barcelona, Fac Med, Dept Fonaments Clin, Barcelona, Spain.;Inst Catalana Recerca & Estudis Avancats ICREA, Barcelona, Spain.
(author)
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Inst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain.;CIBERONC, Ctr Invest Biomed Red Canc, Madrid, Spain.CIBERONC, Ctr Invest Biomed Red Canc, Madrid, Spain.;IDIBAPS, Hosp Clin, Serv Hematol, Barcelona, Spain.
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In:NATURE CANCER: Springer Nature1:11, s. 1066-10812662-1347
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Duran-Ferrer, Ma ...
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Clot, Guillem
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Nadeu, Ferran
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Beekman, Renee
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Baumann, Tycho
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Nordlund, Jessic ...
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Marincevic-Zunig ...
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Lönnerholm, Gudm ...
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Rivas-Delgado, A ...
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Martin, Silvia
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Ordonez, Raquel
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Castellano, Gian ...
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Kulis, Marta
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Queiros, Ana C.
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Lee, Seung-Tae
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Wiemels, Joseph
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Royo, Romina
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Puiggros, Montse ...
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Lu, Junyan
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Gine, Eva
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Bea, Silvia
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Jares, Pedro
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Agirre, Xabier
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Prosper, Felipe
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Lopez-Otin, Carl ...
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Puente, Xose S.
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Oakes, Christoph ...
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Zenz, Thorsten
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Delgado, Julio
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Lopez-Guillermo, ...
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Campo, Elias
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Ignacio Martin-S ...
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