Mar 29, 2020

DNA methylation classification in diffuse glioma shows little spatial heterogeneity after adjusting for tumor purity

BioRxiv : the Preprint Server for Biology
Sam WillcocksRoel GW Verhaak


Intratumoral heterogeneity is a hallmark of diffuse gliomas. We used neuronavigation to acquire 133 image-guided and spatially-separated stereotactic biopsy samples from 16 adult patients with a diffuse glioma, which we characterized using DNA methylation arrays. Samples were obtained from regions with and without imaging abnormalities. Methylation profiles were analyzed to devise a three-dimensional reconstruction of genetic and epigenetic heterogeneity. Molecular aberrations indicated that tumor was found outside imaging abnormalities, underlining the infiltrative nature of this tumor and the limitations of current routine imaging modalities. We demonstrate that tumor purity is highly variable between samples and largely explains apparent epigenetic spatial heterogeneity. Indeed, we observed that DNA methylation subtypes are highly conserved in space after adjusting for tumor purity. Genome-wide heterogeneity analysis showed equal or increased heterogeneity among normal tissue when compared to tumor. These findings were validated in a separate cohort of 61 multi-sector tumor and 64 normal samples. Our findings underscore the infiltrative nature of diffuse gliomas and suggest that heterogeneity in DNA methylation is innate to ...Continue Reading

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Mentioned in this Paper

Genome-Wide Association Study
Primer Extension
Genetic Analysis
Genetic Screening Method
Nucleic Acid Sequencing
Massively-Parallel Sequencing
Doxorubicin/Semustine/Streptozocin Protocol
Oligonucleotide Primers

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