PT  - JOURNAL ARTICLE
AU  - Johanna Klughammer
AU  - Barbara Kiesel
AU  - Thomas Roetzer
AU  - Nikolaus Fortelny
AU  - Amelie Kuchler
AU  - Nathan C. Sheffield
AU  - Paul Datlinger
AU  - Nadine Peter
AU  - Karl-Heinz Nenning
AU  - Julia Furtner
AU  - Martha Nowosielski
AU  - Marco Augustin
AU  - Mario Mischkulnig
AU  - Thomas Ströbel
AU  - Patrizia Moser
AU  - Christian F. Freyschlag
AU  - Johannes Kerschbaumer
AU  - Claudius Thomé
AU  - Astrid E. Grams
AU  - Günther Stockhammer
AU  - Melitta Kitzwoegerer
AU  - Stefan Oberndorfer
AU  - Franz Marhold
AU  - Serge Weis
AU  - Johannes Trenkler
AU  - Johanna Buchroithner
AU  - Josef Pichler
AU  - Johannes Haybaeck
AU  - Stefanie Krassnig
AU  - Kariem Madhy Ali
AU  - Gord von Campe
AU  - Franz Payer
AU  - Camillo Sherif
AU  - Julius Preiser
AU  - Thomas Hauser
AU  - Peter A. Winkler
AU  - Waltraud Kleindienst
AU  - Franz Würtz
AU  - Tanisa Brandner-Kokalj
AU  - Martin Stultschnig
AU  - Stefan Schweiger
AU  - Karin Dieckmann
AU  - Matthias Preusser
AU  - Georg Langs
AU  - Bernhard Baumann
AU  - Engelbert Knosp
AU  - Georg Widhalm
AU  - Christine Marosi
AU  - Johannes A. Hainfellner
AU  - Adelheid Woehrer
AU  - Christoph Bock
TI  - The DNA methylation landscape of glioblastoma disease progression shows extensive heterogeneity in time and space
AID  - 10.1101/173864
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 173864
4099  - http://biorxiv.org/content/early/2017/08/09/173864.short
4100  - http://biorxiv.org/content/early/2017/08/09/173864.full
AB  - 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 the DNA methylation dynamics in matched primary and recurring glioblastoma tumors, based on a national population registry and a comprehensively annotated clinical cohort. We demonstrate the feasibility of DNA methylation mapping in a large set of routinely collected formalin-fixed paraffin-embedded (FFPE) samples, and we validate bisulfite sequencing as a multi-purpose assay that allowed us to infer a range of different genetic, epigenetic, and transcriptional tumor characteristics. Based on these data, we identified characteristic 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 provides a resource for dissecting DNA methylation heterogeneity in genetically diverse and heterogeneous tumors, and it demonstrates the feasibility of integrating epigenomics, radiology, and digital pathology in a representative national cohort, leveraging samples and data collected as part of routine clinical practice.