Document Type

Article

Publication Date

12-1-2021

Publication Title

Neuro Oncol

Keywords

JGM, Adult, Brain Neoplasms, DNA Methylation, Glioma, Humans, Isocitrate Dehydrogenase, Mutation, Oligodendroglioma

JAX Source

Neuro Oncol 2021 Dec; 23(12):2054-2065

Volume

23

Issue

12

First Page

2054

Last Page

2065

ISSN

1523-5866

PMID

34049406

DOI

https://doi.org/10.1093/neuonc/noab134

Grant

CA034196

Abstract

BACKGROUND: Intratumoral heterogeneity is a hallmark of diffuse gliomas. DNA methylation profiling is an emerging approach in the clinical classification of brain tumors. The goal of this study is to investigate the effects of intratumoral heterogeneity on classification confidence.

METHODS: We used neuronavigation to acquire 133 image-guided and spatially separated stereotactic biopsy samples from 16 adult patients with a diffuse glioma (7 IDH-wildtype and 2 IDH-mutant glioblastoma, 6 diffuse astrocytoma, IDH-mutant and 1 oligodendroglioma, IDH-mutant and 1p19q codeleted), which we characterized using DNA methylation arrays. Samples were obtained from regions with and without abnormalities on contrast-enhanced T1-weighted and fluid-attenuated inversion recovery MRI. Methylation profiles were analyzed to devise a 3-dimensional reconstruction of (epi)genetic heterogeneity. Tumor purity was assessed from clonal methylation sites.

RESULTS: 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 explains a substantial part of apparent epigenetic spatial heterogeneity. We observed that DNA methylation subtypes are often, but not always, conserved in space taking tumor purity and prediction accuracy into account.

CONCLUSION: Our results underscore the infiltrative nature of diffuse gliomas and suggest that DNA methylation subtypes are relatively concordant in this tumor type, although some heterogeneity exists.

Comments

This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License

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