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.
Authors	Matthew Bott, Marie Brevet, Barry S Taylor, Shigeki Shimizu, Tatsuo Ito, Lu Wang, Jenette Creaney, Richard A Lake, Maureen F Zakowski, Boris Reva, Chris Sander, Robert Delsite, Simon Powell, Qin Zhou, Ronglai Shen, Adam Olshen, Valerie Rusch, Marc Ladanyi
Journal	Nature genetics (Nat Genet) Vol. 43 Issue 7 Pg. 668-72 (Jun 05 2011) ISSN: 1546-1718 [Electronic] United States
PMID	21642991 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	BAP1 protein, human E2F Transcription Factors Polycomb-Group Proteins RNA, Messenger Repressor Proteins Tumor Suppressor Proteins Ubiquitin Thiolesterase
Topics	Adult Aged Apoptosis Blotting, Western Cell Nucleus (enzymology, genetics) Cell Proliferation Chromosomes, Human, Pair 3 (genetics) E2F Transcription Factors (genetics, metabolism) Female Humans Immunoenzyme Techniques Immunoprecipitation Male Mesothelioma (genetics, pathology) Middle Aged Mutation (genetics) Pleural Neoplasms (genetics, pathology) Polycomb-Group Proteins RNA, Messenger (genetics) Repressor Proteins (genetics, metabolism) Reverse Transcriptase Polymerase Chain Reaction Tumor Cells, Cultured Tumor Suppressor Proteins (genetics) Ubiquitin Thiolesterase (genetics)

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