The nuclear deubiquitinase BAP1 is commonly inactivated by somatic mutations and 3p21.1 losses in malignant pleural mesothelioma
By M. Bott, M. Brevet, Barry S. Taylor, S. Shimizu, Tatsuo Ito, Lu Wang, J. Creaney, R. Lake, M. Zakowski, B. Reva and 8 more. Nature Genetics, 2011
668 citations recorded by the source corpus.
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.
Subfields: Genetics, Molecular Biology, Pulmonary and Respiratory Medicine
View Paper: https://www.semanticscholar.org/paper/13e84d8cf9fdf456ee7bc68a111df2545a996bd6
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In Genetics
- Ronglai Shen
- Venkatraman E. Seshan
- Christopher Sander
- K. Helin
- Luciano Di Croce
- Nicholas McGranahan
- Charles Swanton
- Piotr Fryzlewicz
In Molecular Biology
- Ronglai Shen
- Luciano Di Croce
- Venkatraman E. Seshan
- Marc Ladanyi
- Nikolaus Schultz
- Christopher Sander
- K. Helin
- Debora Marks
In Pulmonary and Respiratory Medicine
Citations in the corpus
- Pattern discovery and cancer gene identification in integrated cancer genomic data (2013, background): “By Fisher ’ s combined probability test, the top-ranking genes in cluster 1 that show selective copy number loss and underexpression include two tumor suppressor genes, XPC and BAP1 , which have been previously linked to lung cancer (20) and mesothelioma (21).”
- Transcriptional regulation by Polycomb group proteins (2013, background): “; and from the Novo Nordisk Foundation, the Danish Cancer Society and the Danish Council for Strategic Research (12-110503) to K.”