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Integrative Molecular Characterization of Malignant Pleural Mesothelioma.

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cam.issuedOnline2018-10-15
dc.contributor.authorHmeljak, Julija
dc.contributor.authorSanchez-Vega, Francisco
dc.contributor.authorHoadley, Katherine A
dc.contributor.authorShih, Juliann
dc.contributor.authorStewart, Chip
dc.contributor.authorHeiman, David
dc.contributor.authorTarpey, Patrick
dc.contributor.authorDanilova, Ludmila
dc.contributor.authorDrill, Esther
dc.contributor.authorGibb, Ewan A
dc.contributor.authorBowlby, Reanne
dc.contributor.authorKanchi, Rupa
dc.contributor.authorOsmanbeyoglu, Hatice U
dc.contributor.authorSekido, Yoshitaka
dc.contributor.authorTakeshita, Jumpei
dc.contributor.authorNewton, Yulia
dc.contributor.authorGraim, Kiley
dc.contributor.authorGupta, Manaswi
dc.contributor.authorGay, Carl M
dc.contributor.authorDiao, Lixia
dc.contributor.authorGibbs, David L
dc.contributor.authorThorsson, Vesteinn
dc.contributor.authorIype, Lisa
dc.contributor.authorKantheti, Havish
dc.contributor.authorSeverson, David T
dc.contributor.authorRavegnini, Gloria
dc.contributor.authorDesmeules, Patrice
dc.contributor.authorJungbluth, Achim A
dc.contributor.authorTravis, William D
dc.contributor.authorDacic, Sanja
dc.contributor.authorChirieac, Lucian R
dc.contributor.authorGalateau-Sallé, Françoise
dc.contributor.authorFujimoto, Junya
dc.contributor.authorHusain, Aliya N
dc.contributor.authorSilveira, Henrique C
dc.contributor.authorRusch, Valerie W
dc.contributor.authorRintoul, Robert C
dc.contributor.authorPass, Harvey
dc.contributor.authorKindler, Hedy
dc.contributor.authorZauderer, Marjorie G
dc.contributor.authorKwiatkowski, David J
dc.contributor.authorBueno, Raphael
dc.contributor.authorTsao, Anne S
dc.contributor.authorCreaney, Jenette
dc.contributor.authorLichtenberg, Tara
dc.contributor.authorLeraas, Kristen
dc.contributor.authorBowen, Jay
dc.contributor.authorTCGA Research Network
dc.contributor.authorFelau, Ina
dc.contributor.authorZenklusen, Jean Claude
dc.contributor.authorAkbani, Rehan
dc.contributor.authorCherniack, Andrew D
dc.contributor.authorByers, Lauren A
dc.contributor.authorNoble, Michael S
dc.contributor.authorFletcher, Jonathan A
dc.contributor.authorRobertson, A Gordon
dc.contributor.authorShen, Ronglai
dc.contributor.authorAburatani, Hiroyuki
dc.contributor.authorRobinson, Bruce W
dc.contributor.authorCampbell, Peter
dc.contributor.authorLadanyi, Marc
dc.contributor.orcidHoadley, Katherine A [0000-0002-1216-477X]
dc.contributor.orcidStewart, Chip [0000-0003-2245-9552]
dc.contributor.orcidDanilova, Ludmila [0000-0003-2813-3094]
dc.contributor.orcidNewton, Yulia [0000-0002-6874-4335]
dc.contributor.orcidSeverson, David T [0000-0002-1750-8332]
dc.contributor.orcidRavegnini, Gloria [0000-0002-7774-402X]
dc.contributor.orcidSilveira, Henrique C [0000-0001-8607-6206]
dc.contributor.orcidRintoul, Robert C [0000-0003-3875-3780]
dc.contributor.orcidZauderer, Marjorie G [0000-0002-6109-5790]
dc.contributor.orcidKwiatkowski, David J [0000-0002-5668-5219]
dc.contributor.orcidTsao, Anne S [0000-0003-0505-6639]
dc.contributor.orcidCherniack, Andrew D [0000-0003-0470-0111]
dc.date.accessioned2018-12-18T00:31:38Z
dc.date.available2018-12-18T00:31:38Z
dc.date.issued2018-12
dc.description.abstractMalignant pleural mesothelioma (MPM) is a highly lethal cancer of the lining of the chest cavity. To expand our understanding of MPM, we conducted a comprehensive integrated genomic study, including the most detailed analysis of BAP1 alterations to date. We identified histology-independent molecular prognostic subsets, and defined a novel genomic subtype with TP53 and SETDB1 mutations and extensive loss of heterozygosity. We also report strong expression of the immune-checkpoint gene VISTA in epithelioid MPM, strikingly higher than in other solid cancers, with implications for the immune response to MPM and for its immunotherapy. Our findings highlight new avenues for further investigation of MPM biology and novel therapeutic options. SIGNIFICANCE: Through a comprehensive integrated genomic study of 74 MPMs, we provide a deeper understanding of histology-independent determinants of aggressive behavior, define a novel genomic subtype with TP53 and SETDB1 mutations and extensive loss of heterozygosity, and discovered strong expression of the immune-checkpoint gene VISTA in epithelioid MPM.See related commentary by Aggarwal and Albelda, p. 1508.This article is highlighted in the In This Issue feature, p. 1494.
dc.format.mediumPrint-Electronic
dc.identifier.doi10.17863/CAM.34374
dc.identifier.eissn2159-8290
dc.identifier.issn2159-8274
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/287064
dc.languageeng
dc.language.isoeng
dc.publisherAmerican Association for Cancer Research (AACR)
dc.publisher.urlhttp://dx.doi.org/10.1158/2159-8290.cd-18-0804
dc.subjectAged
dc.subjectBiomarkers, Tumor
dc.subjectFemale
dc.subjectHistone-Lysine N-Methyltransferase
dc.subjectHumans
dc.subjectKaplan-Meier Estimate
dc.subjectLung Neoplasms
dc.subjectMale
dc.subjectMesothelioma
dc.subjectMiddle Aged
dc.subjectMutation
dc.subjectPleural Neoplasms
dc.subjectPrognosis
dc.subjectProtein Methyltransferases
dc.subjectTumor Suppressor Proteins
dc.subjectUbiquitin Thiolesterase
dc.titleIntegrative Molecular Characterization of Malignant Pleural Mesothelioma.
dc.typeArticle
dcterms.dateAccepted2018-10-10
prism.endingPage1565
prism.issueIdentifier12
prism.publicationDate2018
prism.publicationNameCancer Discov
prism.startingPage1548
prism.volume8
rioxxterms.licenseref.startdate2018-12
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.typeJournal Article/Review
rioxxterms.versionAM
rioxxterms.versionofrecord10.1158/2159-8290.CD-18-0804

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