Cross-species transcriptional analysis reveals conserved and host-specific neoplastic processes in mammalian glioma

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dc.contributor.authorConnolly, Nina P.en
dc.contributor.authorShetty, Amol C.en
dc.contributor.authorStokum, Jesse A.en
dc.contributor.authorHoeschele, Inaen
dc.contributor.authorSiegel, Marni B.en
dc.contributor.authorMiller, C. Ryanen
dc.contributor.authorKim, Anthony J.en
dc.contributor.authorHo, Cheng-Yingen
dc.contributor.authorDavila, Eduardoen
dc.contributor.authorSimard, J. Marcen
dc.contributor.authorDevine, Scott E.en
dc.contributor.authorRossmeisl, John H. Jr.en
dc.contributor.authorHolland, Eric C.en
dc.contributor.authorWinkles, Jeffrey A.en
dc.contributor.authorWoodworth, Graeme F.en
dc.contributor.departmentSmall Animal Clinical Sciencesen
dc.contributor.departmentStatisticsen
dc.contributor.departmentFralin Life Sciences Instituteen
dc.date.accessioned2018-12-21T14:55:34Zen
dc.date.available2018-12-21T14:55:34Zen
dc.date.issued2018-01-19en
dc.description.abstractGlioma is a unique neoplastic disease that develops exclusively in the central nervous system (CNS) and rarely metastasizes to other tissues. This feature strongly implicates the tumor-host CNS microenvironment in gliomagenesis and tumor progression. We investigated the differences and similarities in glioma biology as conveyed by transcriptomic patterns across four mammalian hosts: rats, mice, dogs, and humans. Given the inherent intra-tumoral molecular heterogeneity of human glioma, we focused this study on tumors with upregulation of the platelet-derived growth factor signaling axis, a common and early alteration in human gliomagenesis. The results reveal core neoplastic alterations in mammalian glioma, as well as unique contributions of the tumor host to neoplastic processes. Notable differences were observed in gene expression patterns as well as related biological pathways and cell populations known to mediate key elements of glioma biology, including angiogenesis, immune evasion, and brain invasion. These data provide new insights regarding mammalian models of human glioma, and how these insights and models relate to our current understanding of the human disease.en
dc.description.notesThis study was supported by NIH T32 CA154274 (NC), NIH F30-CA200345-01 (MBS), NIH R01CA139099 (JHR); the Wallace Coulter Foundation (JHR); the Passano Foundation (GW); NIH K12 NS080223 Neurosurgeon Research Career Development Program (GW), NIH K08 NS090430 (GW), American Cancer Society-Research Scholar Grant 128970-RSG-16-012-01-CDD (GW).en
dc.description.sponsorshipNIH [T32 CA154274, F30-CA200345-01, R01CA139099, K12 NS080223, K08 NS090430]; Wallace Coulter Foundation; Passano Foundation; American Cancer Society-Research Scholar Grant [128970-RSG-16-012-01-CDD]en
dc.description.versionPublished versionen
dc.format.extent15 pagesen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1038/s41598-018-19451-6en
dc.identifier.issn2045-2322en
dc.identifier.other1180en
dc.identifier.pmid29352201en
dc.identifier.urihttp://hdl.handle.net/10919/86491en
dc.identifier.volume8en
dc.language.isoenen
dc.publisherSpringer Natureen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectglioblastoma stem-cellsen
dc.subjectgrowth-factor receptoren
dc.subjectbrain-tumorsen
dc.subjectnatural-historyen
dc.subjectmurine modelsen
dc.subjectin-vivoen
dc.subjectprecursor cellsen
dc.subjecttransgenic ratsen
dc.subjectcanine gliomasen
dc.subjectmouse modelsen
dc.titleCross-species transcriptional analysis reveals conserved and host-specific neoplastic processes in mammalian gliomaen
dc.title.serialScientific Reportsen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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