TET CpG sequence-context-specific DNA demethylation shapes progression of IDH-mutant gliomas.
retrospective_cohort · Level III
Where this comes from
- Record sourced from PubMed, PMID 41850239.
- Also identified by DOI 10.1016/j.xcrm.2026.102682 and PMC identifier 13006442.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Treatment decisions in IDH-mutant oligodendrogliomas are shaped by tumor aggressiveness, underscoring the need for objective grading of these malignant brain tumors. We collect 302 primary and recurrent resections from oligodendrogliomas and perform Ki-67 staining, proteomics, and DNA methylation profiling. During tumor progression, DNA methylation of oligodendrogliomas changes along a continuum. This continuum is linked to increased epigenetic aging, methylation of transcription factors and Ki-67+ cell density, and large-scale DNA demethylation. Demethylation correlates with CpG flanking sequences preferred by TET enzymes. We confirm these findings in previously profiled astrocytomas, indicating IDH-mutant gliomas progress along a shared epigenetic axis. We develop an objective DNA methylation-based prognostic continuous grading coefficient (CGC<sup>ψ</sup>) that captures these changes and outperforms the World Health Organization (WHO) grading for oligodendrogliomas. Our findings underscore the potential of DNA methylation-based grading to more accurately reflect tumor biology and inform clinical decision-making in IDH-mutant gliomas.
Medical subject headings
- Isocitrate Dehydrogenase
- CpG Islands
- Mutation
- Glioma
- Brain Neoplasms
- DNA Demethylation
- Oligodendroglioma
- Proto-Oncogene Proteins