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.
- Type: Other
- Archiver: European Genome-Phenome Archive (EGA)
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 |
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The DNA methylation landscape of glioblastoma disease progression shows extensive heterogeneity in time and space.
Nat Med 24: 2018 1611-1624 |
159 |
DNA CpG methylation in sequential glioblastoma specimens.
J Cancer Res Clin Oncol 146: 2020 2885-2896 |
7 |
Involvement of the Catecholamine Pathway in Glioblastoma Development.
Cells 10: 2021 549 |
5 |
Discovery of Candidate DNA Methylation Cancer Driver Genes.
Cancer Discov 11: 2021 2266-2281 |
34 |
Epigenetic Suppression of the IL-7 Pathway in Progressive Glioblastoma.
Biomedicines 10: 2022 2174 |
4 |