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Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
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Spatial concordance of DNA methylation classification in diffuse glioma
Niels Verburg1,2, Floris P Barthel3, Kevin J Anderson3
1Department of Neurosurgery, Amsterdam UMC, Vrije Universiteit, and Brain Tumor Centre, Cancer Center Amsterdam, Amsterdam, the Netherlands.
Neuro-Oncology
|May 28, 2021
Summary
Intratumoral heterogeneity in diffuse gliomas impacts DNA methylation classification. While subtypes are generally consistent, tumor purity variations explain some spatial epigenetic differences, highlighting infiltrative tumor characteristics.
Area of Science:
- Neuro-oncology
- Molecular Pathology
- Cancer Genomics
Background:
- Diffuse gliomas exhibit significant intratumoral heterogeneity.
- DNA methylation profiling is a key tool for brain tumor classification.
- Understanding heterogeneity's impact on classification confidence is crucial.
Purpose of the Study:
- To investigate how intratumoral heterogeneity affects DNA methylation-based classification of diffuse gliomas.
- To analyze the spatial distribution of epigenetic alterations within diffuse gliomas.
Main Methods:
- Acquired 133 spatially separated stereotactic biopsy samples from 16 adult diffuse glioma patients using neuronavigation.
- Characterized samples using DNA methylation arrays and assessed tumor purity.
- Reconstructed 3D (epi)genetic heterogeneity from methylation profiles.
Main Results:
- Identified molecular aberrations outside imaging abnormalities, indicating infiltrative tumor growth.
- Demonstrated high variability in tumor purity, explaining significant epigenetic heterogeneity.
- Observed that DNA methylation subtypes are generally conserved spatially, considering purity and prediction accuracy.
Conclusions:
- Diffuse gliomas are infiltrative, with molecular alterations extending beyond imaging visible regions.
- DNA methylation subtypes show relative spatial concordance in diffuse gliomas, despite existing heterogeneity.
