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Transcriptomic Characterization of SF3B1 Mutation Reveals Its Pleiotropic Effects in Chronic Lymphocytic Leukemia.
Wang, Lili; Brooks, Angela N; Fan, Jean; Wan, Youzhong; Gambe, Rutendo; Li, Shuqiang; Hergert, Sarah; Yin, Shanye; Freeman, Samuel S; Levin, Joshua Z; Fan, Lin; Seiler, Michael; Buonamici, Silvia; Smith, Peter G; Chau, Kevin F; Cibulskis, Carrie L; Zhang, Wandi; Rassenti, Laura Z; Ghia, Emanuela M; Kipps, Thomas J; Fernandes, Stacey; Bloch, Donald B; Kotliar, Dylan; Landau, Dan A; Shukla, Sachet A; Aster, Jon C; Reed, Robin; DeLuca, David S; Brown, Jennifer R; Neuberg, Donna; Getz, Gad; Livak, Kenneth J; Meyerson, Matthew M; Kharchenko, Peter V; Wu, Catherine J.
Afiliación
  • Wang L; Department of Medical Oncology, Dana-Farber Cancer Institute, Dana 540, 44 Binney Street, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA.
  • Brooks AN; Department of Medical Oncology, Dana-Farber Cancer Institute, Dana 540, 44 Binney Street, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02141, USA; University of California, Santa Cruz, CA 95064, USA.
  • Fan J; Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA.
  • Wan Y; Department of Medical Oncology, Dana-Farber Cancer Institute, Dana 540, 44 Binney Street, Boston, MA 02115, USA; National Engineering Laboratory of AIDS Vaccine, School of Life Science, Jilin University, Changchun, Jilin, PRC.
  • Gambe R; Department of Medical Oncology, Dana-Farber Cancer Institute, Dana 540, 44 Binney Street, Boston, MA 02115, USA.
  • Li S; Fluidigm Corporation, South San Francisco, CA 94080, USA.
  • Hergert S; Department of Medical Oncology, Dana-Farber Cancer Institute, Dana 540, 44 Binney Street, Boston, MA 02115, USA.
  • Yin S; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
  • Freeman SS; Broad Institute of MIT and Harvard, Cambridge, MA 02141, USA.
  • Levin JZ; Broad Institute of MIT and Harvard, Cambridge, MA 02141, USA.
  • Fan L; Broad Institute of MIT and Harvard, Cambridge, MA 02141, USA.
  • Seiler M; H3 Biomedicine, Cambridge, MA 02141, USA.
  • Buonamici S; H3 Biomedicine, Cambridge, MA 02141, USA.
  • Smith PG; H3 Biomedicine, Cambridge, MA 02141, USA.
  • Chau KF; Harvard Medical School, Boston, MA 02115, USA.
  • Cibulskis CL; Broad Institute of MIT and Harvard, Cambridge, MA 02141, USA.
  • Zhang W; Department of Medical Oncology, Dana-Farber Cancer Institute, Dana 540, 44 Binney Street, Boston, MA 02115, USA.
  • Rassenti LZ; Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
  • Ghia EM; Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
  • Kipps TJ; Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
  • Fernandes S; Department of Medical Oncology, Dana-Farber Cancer Institute, Dana 540, 44 Binney Street, Boston, MA 02115, USA.
  • Bloch DB; Center for Immunology and Inflammatory Disease, Massachusetts General Hospital, Boston, MA 02115, USA.
  • Kotliar D; Harvard Medical School, Boston, MA 02115, USA.
  • Landau DA; Department of Medical Oncology, Dana-Farber Cancer Institute, Dana 540, 44 Binney Street, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA.
  • Shukla SA; Department of Medical Oncology, Dana-Farber Cancer Institute, Dana 540, 44 Binney Street, Boston, MA 02115, USA.
  • Aster JC; Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Reed R; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
  • DeLuca DS; Broad Institute of MIT and Harvard, Cambridge, MA 02141, USA.
  • Brown JR; Department of Medical Oncology, Dana-Farber Cancer Institute, Dana 540, 44 Binney Street, Boston, MA 02115, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Neuberg D; Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
  • Getz G; Broad Institute of MIT and Harvard, Cambridge, MA 02141, USA.
  • Livak KJ; Fluidigm Corporation, South San Francisco, CA 94080, USA.
  • Meyerson MM; Department of Medical Oncology, Dana-Farber Cancer Institute, Dana 540, 44 Binney Street, Boston, MA 02115, USA.
  • Kharchenko PV; Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA.
  • Wu CJ; Department of Medical Oncology, Dana-Farber Cancer Institute, Dana 540, 44 Binney Street, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02141, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA. E
Cancer Cell ; 30(5): 750-763, 2016 Nov 14.
Article en En | MEDLINE | ID: mdl-27818134
Mutations in SF3B1, which encodes a spliceosome component, are associated with poor outcome in chronic lymphocytic leukemia (CLL), but how these contribute to CLL progression remains poorly understood. We undertook a transcriptomic characterization of primary human CLL cells to identify transcripts and pathways affected by SF3B1 mutation. Splicing alterations, identified in the analysis of bulk cells, were confirmed in single SF3B1-mutated CLL cells and also found in cell lines ectopically expressing mutant SF3B1. SF3B1 mutation was found to dysregulate multiple cellular functions including DNA damage response, telomere maintenance, and Notch signaling (mediated through KLF8 upregulation, increased TERC and TERT expression, or altered splicing of DVL2 transcript, respectively). SF3B1 mutation leads to diverse changes in CLL-related pathways.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Fosfoproteínas / Leucemia Linfocítica Crónica de Células B / Empalme Alternativo / Perfilación de la Expresión Génica / Factores de Empalme de ARN / Mutación Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Cancer Cell Asunto de la revista: NEOPLASIAS Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Fosfoproteínas / Leucemia Linfocítica Crónica de Células B / Empalme Alternativo / Perfilación de la Expresión Génica / Factores de Empalme de ARN / Mutación Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Cancer Cell Asunto de la revista: NEOPLASIAS Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos