Evolutionary Trajectories of IDHWT Glioblastomas Reveal a Common Path of Early Tumorigenesis Instigated Years ahead of Initial Diagnosis

Koerber, Verena; Yang, Jing; Barah, Pankaj; Wu, Yonghe; Stichel, Damian; Gu, Zuguang; Fletcher, Michael Nai Chung; Jones, David; Hentschel, Bettina; Lamszus, Katrin; Tonn, Jörg Christian; Schackert, Gabriele; Sabel, Michael; Felsberg, Jörg; Zacher, Angela; Kaulich, Kerstin; Huebschmann, Daniel; Herold-Mende, Christel; Deimling, Andreas von; Weller, Michael; Radlwimmer, Bernhard; Schlesner, Matthias; Reifenberger, Guido; Hoefer, Thomas und Lichter, Peter (2019): Evolutionary Trajectories of IDHWT Glioblastomas Reveal a Common Path of Early Tumorigenesis Instigated Years ahead of Initial Diagnosis. In: Cancer Cell, Bd. 35, Nr. 4

Abstract

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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1535-6108
• Sprache: Englisch