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The DNA methylation landscape of glioblastoma disease progression shows extensive heterogeneity in time and space.


ABSTRACT: Glioblastoma is characterized by widespread genetic and transcriptional heterogeneity, yet little is known about the role of the epigenome in glioblastoma disease progression. Here, we present genome-scale maps of DNA methylation in matched primary and recurring glioblastoma tumors, using data from a highly annotated clinical cohort that was selected through a national patient registry. We demonstrate the feasibility of DNA methylation mapping in a large set of routinely collected FFPE samples, and we validate bisulfite sequencing as a multipurpose assay that allowed us to infer a range of different genetic, epigenetic, and transcriptional characteristics of the profiled tumor samples. On the basis of these data, we identified subtle differences between primary and recurring tumors, links between DNA methylation and the tumor microenvironment, and an association of epigenetic tumor heterogeneity with patient survival. In summary, this study establishes an open resource for dissecting DNA methylation heterogeneity in a genetically diverse and heterogeneous cancer, and it demonstrates the feasibility of integrating epigenomics, radiology, and digital pathology for a national cohort, thereby leveraging existing samples and data collected as part of routine clinical practice.

SUBMITTER: Klughammer J 

PROVIDER: S-EPMC6181207 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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The DNA methylation landscape of glioblastoma disease progression shows extensive heterogeneity in time and space.

Klughammer Johanna J   Kiesel Barbara B   Roetzer Thomas T   Fortelny Nikolaus N   Nemc Amelie A   Nenning Karl-Heinz KH   Furtner Julia J   Sheffield Nathan C NC   Datlinger Paul P   Peter Nadine N   Nowosielski Martha M   Augustin Marco M   Mischkulnig Mario M   Ströbel Thomas T   Alpar Donat D   Ergüner Bekir B   Senekowitsch Martin M   Moser Patrizia P   Freyschlag Christian F CF   Kerschbaumer Johannes J   Thomé Claudius C   Grams Astrid E AE   Stockhammer Günther G   Kitzwoegerer Melitta M   Oberndorfer Stefan S   Marhold Franz F   Weis Serge S   Trenkler Johannes J   Buchroithner Johanna J   Pichler Josef J   Haybaeck Johannes J   Krassnig Stefanie S   Mahdy Ali Kariem K   von Campe Gord G   Payer Franz F   Sherif Camillo C   Preiser Julius J   Hauser Thomas T   Winkler Peter A PA   Kleindienst Waltraud W   Würtz Franz F   Brandner-Kokalj Tanisa T   Stultschnig Martin M   Schweiger Stefan S   Dieckmann Karin K   Preusser Matthias M   Langs Georg G   Baumann Bernhard B   Knosp Engelbert E   Widhalm Georg G   Marosi Christine C   Hainfellner Johannes A JA   Woehrer Adelheid A   Bock Christoph C  

Nature medicine 20180827 10


Glioblastoma is characterized by widespread genetic and transcriptional heterogeneity, yet little is known about the role of the epigenome in glioblastoma disease progression. Here, we present genome-scale maps of DNA methylation in matched primary and recurring glioblastoma tumors, using data from a highly annotated clinical cohort that was selected through a national patient registry. We demonstrate the feasibility of DNA methylation mapping in a large set of routinely collected FFPE samples,  ...[more]

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