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Evolutionary trajectories of IDHWT glioblastomas reveal a common path of early tumorigenesis instigated years ahead of initial diagnosis

Summary - We studied how intratumoral genetic heterogeneity shapes tumor growth and therapy response for isocitrate dehydrogenase (IDH)-wild-type glioblastoma, a rapidly regrowing tumor. We inferred the evolutionary trajectories of matched pairs of primary and relapsed tumors based on deep whole-gen...

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Hauptverfasser: Körber, Verena (VerfasserIn) , Stichel, Damian (VerfasserIn) , Herold-Mende, Christel (VerfasserIn) , Deimling, Andreas von (VerfasserIn) , Radlwimmer, Bernhard (VerfasserIn) , Höfer, Thomas (VerfasserIn) , Lichter, Peter (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 21 March 2019
In: Cancer cell
Year: 2019, Jahrgang: 35, Heft: 4, Pages: 692-704
ISSN:1878-3686
DOI:10.1016/j.ccell.2019.02.007
Online-Zugang:Verlag, Volltext: https://doi.org/10.1016/j.ccell.2019.02.007
Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S1535610819301023
Volltext
Verfasserangaben:Verena Körber, Jing Yang, Pankaj Barah, Yonghe Wu, Damian Stichel, Zuguang Gu, Michael Nai Chung Fletcher, David Jones, Bettina Hentschel, Katrin Lamszus, Jörg Christian Tonn, Gabriele Schackert, Michael Sabel, Jörg Felsberg, Angela Zacher, Kerstin Kaulich, Daniel Hübschmann, Christel Herold-Mende, Andreas von Deimling, Michael Weller, Bernhard Radlwimmer, Matthias Schlesner, Guido Reifenberger, Thomas Höfer, and Peter Lichter
Beschreibung
Zusammenfassung:Summary - We studied how intratumoral genetic heterogeneity shapes tumor growth and therapy response for isocitrate dehydrogenase (IDH)-wild-type glioblastoma, a rapidly regrowing tumor. We inferred the evolutionary trajectories of matched pairs of primary and relapsed tumors based on deep whole-genome-sequencing data. This analysis suggests both a distant origin of de novo glioblastoma, up to 7 years before diagnosis, and a common path of early tumorigenesis, with one or more of chromosome 7 gain, 9p loss, or 10 loss, at tumor initiation. TERT promoter mutations often occurred later as a prerequisite for rapid growth. In contrast to this common early path, relapsed tumors acquired no stereotypical pattern of mutations and typically regrew from oligoclonal origins, suggesting sparse selective pressure by therapeutic measures.
Beschreibung:Gesehen am 17.05.2019
Im Titel ist das WT in IDHWT hochgestellt
Beschreibung:Online Resource
ISSN:1878-3686
DOI:10.1016/j.ccell.2019.02.007

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