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Molecular map of chronic lymphocytic leukemia and its impact on outcome.
Knisbacher, Binyamin A; Lin, Ziao; Hahn, Cynthia K; Nadeu, Ferran; Duran-Ferrer, Martí; Stevenson, Kristen E; Tausch, Eugen; Delgado, Julio; Barbera-Mourelle, Alex; Taylor-Weiner, Amaro; Bousquets-Muñoz, Pablo; Diaz-Navarro, Ander; Dunford, Andrew; Anand, Shankara; Kretzmer, Helene; Gutierrez-Abril, Jesus; López-Tamargo, Sara; Fernandes, Stacey M; Sun, Clare; Sivina, Mariela; Rassenti, Laura Z; Schneider, Christof; Li, Shuqiang; Parida, Laxmi; Meissner, Alexander; Aguet, François; Burger, Jan A; Wiestner, Adrian; Kipps, Thomas J; Brown, Jennifer R; Hallek, Michael; Stewart, Chip; Neuberg, Donna S; Martín-Subero, José I; Puente, Xose S; Stilgenbauer, Stephan; Wu, Catherine J; Campo, Elias; Getz, Gad.
Afiliación
  • Knisbacher BA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Lin Z; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Hahn CK; Harvard University, Cambridge, MA, USA.
  • Nadeu F; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Duran-Ferrer M; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Stevenson KE; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
  • Tausch E; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.
  • Delgado J; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
  • Barbera-Mourelle A; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.
  • Taylor-Weiner A; Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Bousquets-Muñoz P; Department of Internal Medicine III, Ulm University, Ulm, Germany.
  • Diaz-Navarro A; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
  • Dunford A; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.
  • Anand S; Servicio de Hematología, Hospital Clínic, IDIBAPS, Barcelona, Spain.
  • Kretzmer H; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Gutierrez-Abril J; Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA.
  • López-Tamargo S; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Fernandes SM; Departamento de Bioquímica y Biología Molecular, Instituto Universitario de Oncología, Universidad de Oviedo, Oviedo, Spain.
  • Sun C; Departamento de Bioquímica y Biología Molecular, Instituto Universitario de Oncología, Universidad de Oviedo, Oviedo, Spain.
  • Sivina M; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Rassenti LZ; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Schneider C; Department of Genome Regulation, Max Planck Institute for Molecular Genetics, Berlin, Germany.
  • Li S; Computational Oncology Service, Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Parida L; Departamento de Bioquímica y Biología Molecular, Instituto Universitario de Oncología, Universidad de Oviedo, Oviedo, Spain.
  • Meissner A; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Aguet F; Laboratory of Lymphoid Malignancies, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
  • Burger JA; Department of Leukemia, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
  • Wiestner A; Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA.
  • Kipps TJ; Department of Internal Medicine III, Ulm University, Ulm, Germany.
  • Brown JR; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Hallek M; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Stewart C; Translational Immunogenomics Laboratory, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Neuberg DS; IBM Research, Yorktown Heights, NY, USA.
  • Martín-Subero JI; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Puente XS; Department of Genome Regulation, Max Planck Institute for Molecular Genetics, Berlin, Germany.
  • Stilgenbauer S; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.
  • Wu CJ; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Campo E; Department of Leukemia, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
  • Getz G; Laboratory of Lymphoid Malignancies, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Nat Genet ; 54(11): 1664-1674, 2022 11.
Article en En | MEDLINE | ID: mdl-35927489
Recent advances in cancer characterization have consistently revealed marked heterogeneity, impeding the completion of integrated molecular and clinical maps for each malignancy. Here, we focus on chronic lymphocytic leukemia (CLL), a B cell neoplasm with variable natural history that is conventionally categorized into two subtypes distinguished by extent of somatic mutations in the heavy-chain variable region of immunoglobulin genes (IGHV). To build the 'CLL map,' we integrated genomic, transcriptomic and epigenomic data from 1,148 patients. We identified 202 candidate genetic drivers of CLL (109 new) and refined the characterization of IGHV subtypes, which revealed distinct genomic landscapes and leukemogenic trajectories. Discovery of new gene expression subtypes further subcategorized this neoplasm and proved to be independent prognostic factors. Clinical outcomes were associated with a combination of genetic, epigenetic and gene expression features, further advancing our prognostic paradigm. Overall, this work reveals fresh insights into CLL oncogenesis and prognostication.
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Texto completo: 1 Base de datos: MEDLINE Asunto principal: Leucemia Linfocítica Crónica de Células B Tipo de estudio: Prognostic_studies Idioma: En Revista: Nat Genet Asunto de la revista: GENETICA MEDICA Año: 2022 Tipo del documento: Article
Texto completo
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Texto completo: 1 Base de datos: MEDLINE Asunto principal: Leucemia Linfocítica Crónica de Células B Tipo de estudio: Prognostic_studies Idioma: En Revista: Nat Genet Asunto de la revista: GENETICA MEDICA Año: 2022 Tipo del documento: Article