Mario Suvà, MD, PhD

IDH-mutant gliomas are a type of brain tumor that often start as low-grade tumors but become more aggressive over time.

To better understand why, researchers at Mass General Brigham, Weill Cornell Medicine and colleagues looked at serial tumor samples from 19 patients with IDH-mutant gliomas over time to track disease progression.

Using advanced multi-modality single-cell sequencing, they measured changes in individual cancer cells, including DNA methylation (a chemical “tag” on DNA that helps regulate gene activity) and gene expression.

The team, which includes co-senior author Mario Suvà, MD, PhD, of the Department of Pathology and the Krantz Family Center for Cancer Research within the Mass General Brigham Cancer Institute, found that as brain tumors progress, they showed a global loss of DNA methylation in cancer cells, which was associated with a decrease in cancer cell differentiation, while favoring a more aggressive, stem-like tumor state.

Their study thus highlights hypomethylation as a potential marker for prognosis for IDH-mutant gliomas and suggests targets for future therapies. The authors’ approach also offers a blueprint for studying other forms of cancer to better understand their evolution and guide drug development.

Published in Nature Genetics on June 22, 2026 | Read the paper: “Longitudinal changes in DNA methylation in IDH-mutant glioma fuel disease progression through altered cell state differentiation”

Summary reviewed by: Mario L. Suvà, MD, PhD, and Dan Landau, MD, PhD, co-senior authors