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

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.

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID Description Technology Samples
EGAD00001003427 Illumina HiSeq 2000 Illumina HiSeq 3000 Illumina HiSeq 4000 349
EGAD00001004074 Illumina HiSeq 3000 150
EGAD00001004076 Illumina HiSeq 3000 37
EGAD00001004077 Illumina HiSeq 3000 43
Publications Citations
The DNA methylation landscape of glioblastoma disease progression shows extensive heterogeneity in time and space.
Nat Med 24: 2018 1611-1624
DNA CpG methylation in sequential glioblastoma specimens.
J Cancer Res Clin Oncol 146: 2020 2885-2896
Involvement of the Catecholamine Pathway in Glioblastoma Development.
Cells 10: 2021 549
Discovery of Candidate DNA Methylation Cancer Driver Genes.
Cancer Discov 11: 2021 2266-2281
Epigenetic Suppression of the IL-7 Pathway in Progressive Glioblastoma.
Biomedicines 10: 2022 2174