{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1361137043460148736.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1073/pnas.1114817109"}},{"identifier":{"@type":"URI","@value":"https://pnas.org/doi/pdf/10.1073/pnas.1114817109"}}],"dc:title":[{"@value":"Convergent structural alterations define SWItch/Sucrose NonFermentable (SWI/SNF) chromatin remodeler as a central tumor suppressive complex in pancreatic cancer"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:p>Defining the molecular genetic alterations underlying pancreatic cancer may provide unique therapeutic insight for this deadly disease. Toward this goal, we report here an integrative DNA microarray and sequencing-based analysis of pancreatic cancer genomes. Notable among the alterations newly identified, genomic deletions, mutations, and rearrangements recurrently targeted genes encoding components of the SWItch/Sucrose NonFermentable (SWI/SNF) chromatin remodeling complex, including all three putative DNA binding subunits (ARID1A, ARID1B, and PBRM1) and both enzymatic subunits (SMARCA2 and SMARCA4). Whereas alterations of each individual SWI/SNF subunit occurred at modest-frequency, as mutational “hills” in the genomic landscape, together they affected at least one-third of all pancreatic cancers, defining SWI/SNF as a major mutational “mountain.” Consistent with a tumor-suppressive role, re-expression of SMARCA4 in SMARCA4-deficient pancreatic cancer cell lines reduced cell growth and promoted senescence, whereas its overexpression in a SWI/SNF-intact line had no such effect. In addition, expression profiling analyses revealed that SWI/SNF likely antagonizes Polycomb repressive complex 2, implicating this as one possible mechanism of tumor suppression. Our findings reveal SWI/SNF to be a central tumor suppressive complex in pancreatic cancer.</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380013170760907777","@type":"Researcher","foaf:name":[{"@value":"A. Hunter Shain"}],"jpcoar:affiliationName":[{"@value":"Department of Pathology, Stanford University, Stanford, CA 94305;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013170760907778","@type":"Researcher","foaf:name":[{"@value":"Craig P. Giacomini"}],"jpcoar:affiliationName":[{"@value":"Department of Pathology, Stanford University, Stanford, CA 94305;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013170760907779","@type":"Researcher","foaf:name":[{"@value":"Karen Matsukuma"}],"jpcoar:affiliationName":[{"@value":"Department of Pathology, Stanford University, Stanford, CA 94305;"},{"@value":"Departments of bPathology and"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013170760907782","@type":"Researcher","foaf:name":[{"@value":"Collins A. Karikari"}],"jpcoar:affiliationName":[{"@value":"Departments of bPathology and"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013170760907783","@type":"Researcher","foaf:name":[{"@value":"Murali D. Bashyam"}],"jpcoar:affiliationName":[{"@value":"Laboratory of Molecular Oncology, Centre for DNA Fingerprinting and Diagnostics, Nampally, Hyderabad 500001, India; and"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013170760907776","@type":"Researcher","foaf:name":[{"@value":"Manuel Hidalgo"}],"jpcoar:affiliationName":[{"@value":"Oncology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21231;"},{"@value":"Clinical Research Program, Centro Nacional de Investigaciones Oncológicas, E-28029 Madrid, Spain"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013170760907781","@type":"Researcher","foaf:name":[{"@value":"Anirban Maitra"}],"jpcoar:affiliationName":[{"@value":"Departments of bPathology and"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013170760907780","@type":"Researcher","foaf:name":[{"@value":"Jonathan R. Pollack"}],"jpcoar:affiliationName":[{"@value":"Department of Pathology, Stanford University, Stanford, CA 94305;"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"00278424"},{"@type":"EISSN","@value":"10916490"}],"prism:publicationName":[{"@value":"Proceedings of the National Academy of Sciences"}],"dc:publisher":[{"@value":"Proceedings of the National Academy of Sciences"}],"prism:publicationDate":"2011-01-10","prism:volume":"109","prism:number":"5","prism:startingPage":"252"},"reviewed":"false","url":[{"@id":"https://pnas.org/doi/pdf/10.1073/pnas.1114817109"}],"createdAt":"2012-01-11","modifiedAt":"2022-06-07","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360002216800937088","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"The chromatin regulator Brg1 suppresses formation of intraductal papillary mucinous neoplasm and pancreatic ductal 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