{"@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/1363670320392012800.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1073/pnas.1121343109"}},{"identifier":{"@type":"URI","@value":"https://pnas.org/doi/pdf/10.1073/pnas.1121343109"}}],"dc:title":[{"@value":"Discovery and prioritization of somatic mutations in diffuse large B-cell lymphoma (DLBCL) by whole-exome sequencing"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:p>\n            To gain insight into the genomic basis of diffuse large B-cell lymphoma (DLBCL), we performed massively parallel whole-exome sequencing of 55 primary tumor samples from patients with DLBCL and matched normal tissue. We identified recurrent mutations in genes that are well known to be functionally relevant in DLBCL, including\n            <jats:italic>MYD88</jats:italic>\n            ,\n            <jats:italic>CARD11</jats:italic>\n            ,\n            <jats:italic>EZH2</jats:italic>\n            , and\n            <jats:italic>CREBBP</jats:italic>\n            . We also identified somatic mutations in genes for which a functional role in DLBCL has not been previously suspected. These genes include\n            <jats:italic>MEF2B</jats:italic>\n            ,\n            <jats:italic>MLL2</jats:italic>\n            ,\n            <jats:italic>BTG1</jats:italic>\n            ,\n            <jats:italic>GNA13</jats:italic>\n            ,\n            <jats:italic>ACTB</jats:italic>\n            ,\n            <jats:italic>P2RY8</jats:italic>\n            ,\n            <jats:italic>PCLO</jats:italic>\n            , and\n            <jats:italic>TNFRSF14</jats:italic>\n            . Further, we show that\n            <jats:italic>BCL2</jats:italic>\n            mutations commonly occur in patients with\n            <jats:italic>BCL2</jats:italic>\n            /\n            <jats:italic>IgH</jats:italic>\n            rearrangements as a result of somatic hypermutation normally occurring at the\n            <jats:italic>IgH</jats:italic>\n            locus. The\n            <jats:italic>BCL2</jats:italic>\n            point mutations are primarily synonymous, and likely caused by activation-induced cytidine deaminase–mediated somatic hypermutation, as shown by comprehensive analysis of enrichment of mutations in WRCY target motifs. Those nonsynonymous mutations that are observed tend to be found outside of the functionally important BH domains of the protein, suggesting that strong negative selection against\n            <jats:italic>BCL2</jats:italic>\n            loss-of-function mutations is at play. Last, by using an algorithm designed to identify likely functionally relevant but infrequent mutations, we identify\n            <jats:italic>KRAS</jats:italic>\n            ,\n            <jats:italic>BRAF</jats:italic>\n            , and\n            <jats:italic>NOTCH1</jats:italic>\n            as likely drivers of DLBCL pathogenesis in some patients. Our data provide an unbiased view of the landscape of mutations in DLBCL, and this in turn may point toward new therapeutic strategies for the disease.\n          </jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380013188114710927","@type":"Researcher","foaf:name":[{"@value":"Jens G. Lohr"}],"jpcoar:affiliationName":[{"@value":"Eli and Edythe Broad Institute, Cambridge, MA 02412;"},{"@value":"Dana–Farber Cancer Institute, Boston, MA 02115;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013188114710917","@type":"Researcher","foaf:name":[{"@value":"Petar Stojanov"}],"jpcoar:affiliationName":[{"@value":"Eli and Edythe Broad Institute, Cambridge, MA 02412;"},{"@value":"Dana–Farber Cancer Institute, Boston, MA 02115;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013188114710919","@type":"Researcher","foaf:name":[{"@value":"Michael S. Lawrence"}],"jpcoar:affiliationName":[{"@value":"Eli and Edythe Broad Institute, Cambridge, MA 02412;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013188114710918","@type":"Researcher","foaf:name":[{"@value":"Daniel Auclair"}],"jpcoar:affiliationName":[{"@value":"Eli and Edythe Broad Institute, Cambridge, MA 02412;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013188114710914","@type":"Researcher","foaf:name":[{"@value":"Bjoern Chapuy"}],"jpcoar:affiliationName":[{"@value":"Dana–Farber Cancer Institute, Boston, MA 02115;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013188114710944","@type":"Researcher","foaf:name":[{"@value":"Carrie Sougnez"}],"jpcoar:affiliationName":[{"@value":"Eli and Edythe Broad Institute, Cambridge, MA 02412;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013188114710929","@type":"Researcher","foaf:name":[{"@value":"Peter Cruz-Gordillo"}],"jpcoar:affiliationName":[{"@value":"Eli and Edythe Broad Institute, Cambridge, MA 02412;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013188114710923","@type":"Researcher","foaf:name":[{"@value":"Birgit Knoechel"}],"jpcoar:affiliationName":[{"@value":"Eli and Edythe Broad Institute, Cambridge, MA 02412;"},{"@value":"Dana–Farber Cancer Institute, Boston, MA 02115;"},{"@value":"Children's Hospital Boston, Boston, MA 02115;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013188114710922","@type":"Researcher","foaf:name":[{"@value":"Yan W. Asmann"}],"jpcoar:affiliationName":[{"@value":"Mayo Clinic College of Medicine, Rochester, MN 55902;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013188114710943","@type":"Researcher","foaf:name":[{"@value":"Susan L. Slager"}],"jpcoar:affiliationName":[{"@value":"Mayo Clinic College of Medicine, Rochester, MN 55902;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013188114710939","@type":"Researcher","foaf:name":[{"@value":"Anne J. Novak"}],"jpcoar:affiliationName":[{"@value":"Mayo Clinic College of Medicine, Rochester, MN 55902;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013188114710928","@type":"Researcher","foaf:name":[{"@value":"Ahmet Dogan"}],"jpcoar:affiliationName":[{"@value":"Mayo Clinic College of Medicine, Rochester, MN 55902;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013188114710940","@type":"Researcher","foaf:name":[{"@value":"Stephen M. Ansell"}],"jpcoar:affiliationName":[{"@value":"Mayo Clinic College of Medicine, Rochester, MN 55902;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013188114710932","@type":"Researcher","foaf:name":[{"@value":"Brian K. Link"}],"jpcoar:affiliationName":[{"@value":"University of Iowa College of Medicine, Iowa City, IA 52245;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013188114710915","@type":"Researcher","foaf:name":[{"@value":"Lihua Zou"}],"jpcoar:affiliationName":[{"@value":"Eli and Edythe Broad Institute, Cambridge, MA 02412;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013188114710942","@type":"Researcher","foaf:name":[{"@value":"Joshua Gould"}],"jpcoar:affiliationName":[{"@value":"Eli and Edythe Broad Institute, Cambridge, MA 02412;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013188114710941","@type":"Researcher","foaf:name":[{"@value":"Gordon Saksena"}],"jpcoar:affiliationName":[{"@value":"Eli and Edythe Broad Institute, Cambridge, MA 02412;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013188114710926","@type":"Researcher","foaf:name":[{"@value":"Nicolas Stransky"}],"jpcoar:affiliationName":[{"@value":"Eli and Edythe Broad Institute, Cambridge, MA 02412;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013188114710920","@type":"Researcher","foaf:name":[{"@value":"Claudia Rangel-Escareño"}],"jpcoar:affiliationName":[{"@value":"Instituto Nacional de Medicina Genómica, 14610 Mexico DF, Mexico;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013188114710933","@type":"Researcher","foaf:name":[{"@value":"Juan Carlos Fernandez-Lopez"}],"jpcoar:affiliationName":[{"@value":"Instituto Nacional de Medicina Genómica, 14610 Mexico DF, Mexico;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013188114710930","@type":"Researcher","foaf:name":[{"@value":"Alfredo Hidalgo-Miranda"}],"jpcoar:affiliationName":[{"@value":"Instituto Nacional de Medicina Genómica, 14610 Mexico DF, Mexico;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013188114710921","@type":"Researcher","foaf:name":[{"@value":"Jorge Melendez-Zajgla"}],"jpcoar:affiliationName":[{"@value":"Instituto Nacional de Medicina Genómica, 14610 Mexico DF, Mexico;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013188114710912","@type":"Researcher","foaf:name":[{"@value":"Enrique Hernández-Lemus"}],"jpcoar:affiliationName":[{"@value":"Instituto Nacional de Medicina Genómica, 14610 Mexico DF, Mexico;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013188114710924","@type":"Researcher","foaf:name":[{"@value":"Angela Schwarz-Cruz y Celis"}],"jpcoar:affiliationName":[{"@value":"Instituto Nacional de Medicina Genómica, 14610 Mexico DF, Mexico;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013188114710916","@type":"Researcher","foaf:name":[{"@value":"Ivan Imaz-Rosshandler"}],"jpcoar:affiliationName":[{"@value":"Instituto Nacional de Medicina Genómica, 14610 Mexico DF, Mexico;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013188114710945","@type":"Researcher","foaf:name":[{"@value":"Akinyemi I. Ojesina"}],"jpcoar:affiliationName":[{"@value":"Eli and Edythe Broad Institute, Cambridge, MA 02412;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013188114710934","@type":"Researcher","foaf:name":[{"@value":"Joonil Jung"}],"jpcoar:affiliationName":[{"@value":"Eli and Edythe Broad Institute, Cambridge, MA 02412;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013188114710937","@type":"Researcher","foaf:name":[{"@value":"Chandra S. Pedamallu"}],"jpcoar:affiliationName":[{"@value":"Eli and Edythe Broad Institute, Cambridge, MA 02412;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013188114710935","@type":"Researcher","foaf:name":[{"@value":"Eric S. Lander"}],"jpcoar:affiliationName":[{"@value":"Eli and Edythe Broad Institute, Cambridge, MA 02412;"},{"@value":"Harvard Medical School, Boston, MA 02115;"},{"@value":"Massachusetts Institute of Technology, Cambridge, MA 02142; and"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013188114710938","@type":"Researcher","foaf:name":[{"@value":"Thomas M. Habermann"}],"jpcoar:affiliationName":[{"@value":"Mayo Clinic College of Medicine, Rochester, MN 55902;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013188114710931","@type":"Researcher","foaf:name":[{"@value":"James R. Cerhan"}],"jpcoar:affiliationName":[{"@value":"Mayo Clinic College of Medicine, Rochester, MN 55902;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013188114710913","@type":"Researcher","foaf:name":[{"@value":"Margaret A. Shipp"}],"jpcoar:affiliationName":[{"@value":"Dana–Farber Cancer Institute, Boston, MA 02115;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013188114710936","@type":"Researcher","foaf:name":[{"@value":"Gad Getz"}],"jpcoar:affiliationName":[{"@value":"Eli and Edythe Broad Institute, Cambridge, MA 02412;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013188114710925","@type":"Researcher","foaf:name":[{"@value":"Todd R. Golub"}],"jpcoar:affiliationName":[{"@value":"Eli and Edythe Broad Institute, Cambridge, MA 02412;"},{"@value":"Dana–Farber Cancer Institute, Boston, MA 02115;"},{"@value":"Harvard Medical School, Boston, MA 02115;"},{"@value":"Howard Hughes Medical Institute, Chevy Chase, MD 20815"}]}],"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":"2012-02-17","prism:volume":"109","prism:number":"10","prism:startingPage":"3879","prism:endingPage":"3884"},"reviewed":"false","url":[{"@id":"https://pnas.org/doi/pdf/10.1073/pnas.1121343109"}],"createdAt":"2012-02-18","modifiedAt":"2022-06-07","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1050285299888389888","@type":"Article","resourceType":"学術雑誌論文(journal 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