The nuclear deubiquitinase BAP1 is commonly inactivated by somatic mutations and 3p21.1 losses in malignant pleural mesothelioma Journal Article


Authors: Bott, M.; Brevet, M.; Taylor, B. S.; Shimizu, S.; Ito, T.; Wang, L.; Creaney, J.; Lake, R. A.; Zakowski, M. F.; Reva, B.; Sander, C.; Delsite, R.; Powell, S.; Zhou, Q.; Shen, R.; Olshen, A.; Rusch, V.; Ladanyi, M.
Article Title: The nuclear deubiquitinase BAP1 is commonly inactivated by somatic mutations and 3p21.1 losses in malignant pleural mesothelioma
Abstract: Malignant pleural mesotheliomas (MPMs) often show CDKN2A and NF2 inactivation, but other highly recurrent mutations have not been described. To identify additional driver genes, we used an integrated genomic analysis of 53 MPM tumor samples to guide a focused sequencing effort that uncovered somatic inactivating mutations in BAP1 in 23% of MPMs. The BAP1 nuclear deubiquitinase is known to target histones (together with ASXL1 as a Polycomb repressor subunit) and the HCF1 transcriptional co-factor, and we show that BAP1 knockdown in MPM cell lines affects E2F and Polycomb target genes. These findings implicate transcriptional deregulation in the pathogenesis of MPM. © 2011 Nature America, Inc. All rights reserved.
Keywords: adult; controlled study; human tissue; human cell; somatic mutation; pathogenesis; conference paper; gene; embryo; genome analysis; histone; transcription factor e2f; nucleotide sequence; tumor cell line; pleura mesothelioma; gene inactivation; gene silencing; chromosome 3p; polycomb group protein; brca1 associated ring domain protein 1; bap1 gene
Journal Title: Nature Genetics
Volume: 43
Issue: 7
ISSN: 1061-4036
Publisher: Nature Publishing Group  
Date Published: 2011-07-01
Start Page: 668
End Page: 672
Language: English
DOI: 10.1038/ng.855
PROVIDER: scopus
PUBMED: 21642991
PMCID: PMC4643098
DOI/URL:
Notes: --- - "Export Date: 17 August 2011" - "CODEN: NGENE" - "Source: Scopus"
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MSK Authors
  1. Simon Nicholas Powell
    168 Powell
  2. Valerie W Rusch
    656 Rusch
  3. Ronglai Shen
    129 Shen
  4. Shigeki Shimizu
    11 Shimizu
  5. Qin Zhou
    120 Zhou
  6. Marc Ladanyi
    879 Ladanyi
  7. Maureen F Zakowski
    280 Zakowski
  8. Adam B Olshen
    107 Olshen
  9. Lu Wang
    139 Wang
  10. Matthew Bott
    33 Bott
  11. Boris A Reva
    36 Reva
  12. Chris Sander
    196 Sander
  13. Robert Lee Delsite
    11 Delsite
  14. Tatsuo Ito
    8 Ito
  15. Marie Brevet
    11 Brevet
  16. Barry Stephen Taylor
    144 Taylor