Related Experiment Video
Updated: Aug 11, 2025
A Protocol for Explant Cultures of IDH1-mutant Diffuse Low-grade Gliomas
Published on: May 9, 2025
Longitudinal DNA methylation analysis of adult-type IDH-mutant gliomas
Sandra Ferreyra Vega1,2, Thomas Olsson Bontell3,4, Teresia Kling2
1Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Blå Stråket 7, 413 45, Gothenburg, Sweden.
Abstract:
Diffuse gliomas are the most prevalent malignant primary brain tumors in adults and remain incurable despite standard therapy. Tumor recurrence is currently inevitable, which contributes to a persistent high morbidity and mortality in these patients. In this study, we examined the genome-wide DNA methylation profiles of primary and recurrent adult-type IDH-mutant gliomas to elucidate DNA methylation changes associated with tumor progression (with or without malignant transformation). We analyzed DNA methylation profiles of 37 primary IDH-mutant gliomas and 42 paired recurrences using the DNA methylation EPIC beadChip array. DNA methylation-based classification reflected the tumor progression over time. We observed a methylation subtype switch in a proportion of IDH-mutant astrocytomas; the primary tumors were subclassified as low-grade astrocytomas, which progressed to high-grade astrocytomas in the recurrent tumors. The CNS WHO grade 4 IDH-mutant astrocytomas did not always resemble methylation subclasses of higher grades. The number of differentially methylated CpG sites increased over time, and astrocytomas accumulated more differentially methylated CpG sites than oligodendrogliomas during tumor progression. Few differentially methylated CpG sites were shared between patients. We demonstrated that DNA methylation profiles are mostly maintained during IDH-mutant glioma progression, but CpG site-specific methylation alterations can occur.
Insights
DNA methylation profiles in IDH-mutant gliomas largely persist during recurrence. However, specific CpG site alterations occur, reflecting tumor progression and grade changes, particularly in astrocytomas.
Area of Science:
- Neuro-oncology
- Epigenetics
- Genomics
Background:
- Diffuse gliomas are common malignant brain tumors in adults, often incurable with high recurrence rates.
- Tumor recurrence significantly contributes to patient morbidity and mortality.
- Understanding DNA methylation changes during glioma progression is crucial for therapeutic strategies.
Purpose of the Study:
- To investigate genome-wide DNA methylation profiles in primary and recurrent adult-type IDH-mutant gliomas.
- To identify DNA methylation alterations associated with tumor progression and malignant transformation.
- To assess the stability and changes in DNA methylation patterns over time.
Main Methods:
- Analysis of DNA methylation profiles using the DNA methylation EPIC beadChip array.
- Comparison of methylation data from 37 primary IDH-mutant gliomas and 42 paired recurrent tumors.
- DNA methylation-based classification to track tumor progression.
Main Results:
- DNA methylation-based classification accurately reflected tumor progression.
- A subset of IDH-mutant astrocytomas showed a methylation subtype switch from low-grade to high-grade upon recurrence.
- The number of differentially methylated CpG sites increased with time, with astrocytomas accumulating more changes than oligodendrogliomas.
Conclusions:
- DNA methylation profiles are generally maintained during IDH-mutant glioma progression.
- Specific CpG site alterations occur, correlating with tumor progression and grade.
- These findings highlight the dynamic epigenetic landscape of recurrent gliomas.
