| Literature DB >> 27818134 |
Lili Wang1, Angela N Brooks2, Jean Fan3, Youzhong Wan4, Rutendo Gambe5, Shuqiang Li6, Sarah Hergert5, Shanye Yin7, Samuel S Freeman8, Joshua Z Levin8, Lin Fan8, Michael Seiler9, Silvia Buonamici9, Peter G Smith9, Kevin F Chau10, Carrie L Cibulskis8, Wandi Zhang5, Laura Z Rassenti11, Emanuela M Ghia11, Thomas J Kipps11, Stacey Fernandes5, Donald B Bloch12, Dylan Kotliar10, Dan A Landau1, Sachet A Shukla5, Jon C Aster13, Robin Reed7, David S DeLuca8, Jennifer R Brown14, Donna Neuberg15, Gad Getz8, Kenneth J Livak6, Matthew M Meyerson5, Peter V Kharchenko3, Catherine J Wu16.
Abstract
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.Entities:
Keywords: CLL; Notch signaling; RNA sequencing; SF3B1; alternative splicing
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Year: 2016 PMID： 27818134 PMCID： PMC5127278 DOI： 10.1016/j.ccell.2016.10.005
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743