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Mutations driving CLL and their evolution in progression and relapse.
Landau, Dan A; Tausch, Eugen; Taylor-Weiner, Amaro N; Stewart, Chip; Reiter, Johannes G; Bahlo, Jasmin; Kluth, Sandra; Bozic, Ivana; Lawrence, Mike; Böttcher, Sebastian; Carter, Scott L; Cibulskis, Kristian; Mertens, Daniel; Sougnez, Carrie L; Rosenberg, Mara; Hess, Julian M; Edelmann, Jennifer; Kless, Sabrina; Kneba, Michael; Ritgen, Matthias; Fink, Anna; Fischer, Kirsten; Gabriel, Stacey; Lander, Eric S; Nowak, Martin A; Döhner, Hartmut; Hallek, Michael; Neuberg, Donna; Getz, Gad; Stilgenbauer, Stephan; Wu, Catherine J.
Afiliação
  • Landau DA; Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA.
  • Tausch E; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
  • Taylor-Weiner AN; Department of Internal Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
  • Stewart C; Harvard Medical School, Boston, Massachusetts 02115, USA.
  • Reiter JG; Department of Internal Medicine III, Ulm University, Ulm 89081, Germany.
  • Bahlo J; Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA.
  • Kluth S; Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA.
  • Bozic I; Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA.
  • Lawrence M; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
  • Böttcher S; IST Austria (Institute of Science and Technology Austria), Klosterneuburg 3400, Austria.
  • Carter SL; Program for Evolutionary Dynamics, Harvard University, Cambridge 02138, Massachusetts, USA.
  • Cibulskis K; Department I of Internal Medicine and Center of Integrated Oncology Cologne Bonn, University Hospital, Cologne 50937, Germany.
  • Mertens D; Department I of Internal Medicine and Center of Integrated Oncology Cologne Bonn, University Hospital, Cologne 50937, Germany.
  • Sougnez CL; Program for Evolutionary Dynamics, Harvard University, Cambridge 02138, Massachusetts, USA.
  • Rosenberg M; Department of Mathematics, Harvard University, Cambridge, Massachusetts 02138, USA.
  • Hess JM; Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA.
  • Edelmann J; Department of Internal Medicine II, University Hospital of Schleswig-Holstein, Campus Kiel, Kiel 24105, Germany.
  • Kless S; Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA.
  • Kneba M; Joint Center for Cancer Precision Medicine, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02215, USA.
  • Ritgen M; Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA.
  • Fink A; Department of Internal Medicine III, Ulm University, Ulm 89081, Germany.
  • Fischer K; Mechanisms of Leukemogenesis, German Cancer Research Center (DKFZ), Heidelberg 69121, Germany.
  • Gabriel S; Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA.
  • Lander ES; Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA.
  • Nowak MA; Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA.
  • Döhner H; Department of Internal Medicine III, Ulm University, Ulm 89081, Germany.
  • Hallek M; Department of Internal Medicine III, Ulm University, Ulm 89081, Germany.
  • Neuberg D; Department of Internal Medicine II, University Hospital of Schleswig-Holstein, Campus Kiel, Kiel 24105, Germany.
  • Getz G; Department of Internal Medicine II, University Hospital of Schleswig-Holstein, Campus Kiel, Kiel 24105, Germany.
  • Stilgenbauer S; Department I of Internal Medicine and Center of Integrated Oncology Cologne Bonn, University Hospital, Cologne 50937, Germany.
  • Wu CJ; Department I of Internal Medicine and Center of Integrated Oncology Cologne Bonn, University Hospital, Cologne 50937, Germany.
Nature ; 526(7574): 525-30, 2015 Oct 22.
Article em En | MEDLINE | ID: mdl-26466571
ABSTRACT
Which genetic alterations drive tumorigenesis and how they evolve over the course of disease and therapy are central questions in cancer biology. Here we identify 44 recurrently mutated genes and 11 recurrent somatic copy number variations through whole-exome sequencing of 538 chronic lymphocytic leukaemia (CLL) and matched germline DNA samples, 278 of which were collected in a prospective clinical trial. These include previously unrecognized putative cancer drivers (RPS15, IKZF3), and collectively identify RNA processing and export, MYC activity, and MAPK signalling as central pathways involved in CLL. Clonality analysis of this large data set further enabled reconstruction of temporal relationships between driver events. Direct comparison between matched pre-treatment and relapse samples from 59 patients demonstrated highly frequent clonal evolution. Thus, large sequencing data sets of clinically informative samples enable the discovery of novel genes associated with cancer, the network of relationships between the driver events, and their impact on disease relapse and clinical outcome.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Leucemia Linfocítica Crônica de Células B / Progressão da Doença / Evolução Molecular / Mutação / Recidiva Local de Neoplasia Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Humans Idioma: En Revista: Nature Ano de publicação: 2015 Tipo de documento: Article
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Leucemia Linfocítica Crônica de Células B / Progressão da Doença / Evolução Molecular / Mutação / Recidiva Local de Neoplasia Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Humans Idioma: En Revista: Nature Ano de publicação: 2015 Tipo de documento: Article