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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 ...

  • 2020-11-02
  • Springer Nature,2020
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-436028
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-436028URI
  • https://doi.org/10.1038/s43018-020-00131-2DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • 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

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  • Clot, GuillemInst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain.;CIBERONC, Ctr Invest Biomed Red Canc, Madrid, Spain. (author)
  • Nadeu, FerranInst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain.;CIBERONC, Ctr Invest Biomed Red Canc, Madrid, Spain. (author)
  • Beekman, ReneeInst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain.;CIBERONC, Ctr Invest Biomed Red Canc, Madrid, Spain. (author)
  • Baumann, TychoCIBERONC, Ctr Invest Biomed Red Canc, Madrid, Spain.;IDIBAPS, Hosp Clin, Serv Hematol, Barcelona, Spain. (author)
  • Nordlund, JessicaUppsala universitet,Molekylär medicin,Science for Life Laboratory, SciLifeLab(Swepub:uu)jesno775 (author)
  • Marincevic-Zuniga, YanaraUppsala universitet,Molekylär medicin,Science for Life Laboratory, SciLifeLab(Swepub:uu)yanma214 (author)
  • Lönnerholm, Gudmar,1941-Uppsala universitet,Barnneurologi/Barnonkologi(Swepub:uu)gudmarlh (author)
  • Rivas-Delgado, AlfredoInst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain.;IDIBAPS, Hosp Clin, Serv Hematol, Barcelona, Spain. (author)
  • Martin, SilviaInst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain.;CIBERONC, Ctr Invest Biomed Red Canc, Madrid, Spain. (author)
  • Ordonez, RaquelCIBERONC, Ctr Invest Biomed Red Canc, Madrid, Spain.;IDISNA, Ctr Invest Med Aplicada CIMA, Pamplona, Spain. (author)
  • Castellano, GiancarloInst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain. (author)
  • Kulis, MartaInst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain. (author)
  • Queiros, Ana C.Inst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain. (author)
  • Lee, Seung-TaeYonsei Univ, Coll Med, Dept Lab Med, Seoul, South Korea. (author)
  • Wiemels, JosephUniv Southern Calif, Ctr Genet Epidemiol, Los Angeles, CA 90007 USA. (author)
  • Royo, RominaUniv Barcelona, Spanish Natl Bioinformat Inst, Inst Recerca Biomed IRB, Programa Conjunto Biol Computac,Barcelona Superco, Barcelona, Spain. (author)
  • Puiggros, MontserratUniv Barcelona, Spanish Natl Bioinformat Inst, Inst Recerca Biomed IRB, Programa Conjunto Biol Computac,Barcelona Superco, Barcelona, Spain. (author)
  • Lu, JunyanEuropean Mol Biol Lab EMBL, Heidelberg, Germany. (author)
  • 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)
  • 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)
  • 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. (author)
  • Agirre, XabierCIBERONC, Ctr Invest Biomed Red Canc, Madrid, Spain.;IDISNA, Ctr Invest Med Aplicada CIMA, Pamplona, Spain. (author)
  • 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)
  • Lopez-Otin, CarlosCIBERONC, Ctr Invest Biomed Red Canc, Madrid, Spain.;Univ Oviedo, Inst Univ Oncol IUOPA, Dept Bioquim & Biol Mol, Oviedo, Spain. (author)
  • Puente, Xose S.CIBERONC, Ctr Invest Biomed Red Canc, Madrid, Spain.;Univ Oviedo, Inst Univ Oncol IUOPA, Dept Bioquim & Biol Mol, Oviedo, Spain. (author)
  • Oakes, Christopher C.Ohio State Univ, Dept Internal Med, Div Hematol, Columbus, OH 43210 USA. (author)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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. (creator_code:org_t)

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  • In:NATURE CANCER: Springer Nature1:11, s. 1066-10812662-1347

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