Single-cell insights have uncovered the gene driving recurrence and treatment resistance in meningiomas.
Meningiomas are the most common primary brain tumours, accounting for nearly one-third of all central nervous system (CNS) tumours. While most are benign and manageable, 20–30% progress to high-grade forms that behave aggressively, recur frequently, and resist standard treatments. Recurrence remains a major clinical challenge, as these tumours often return stronger, leaving patients with limited therapeutic options. Despite advances in understanding their genetic and molecular profiles, how meningiomas evolve from primary to recurrent states has remained unclear.
New study uses single-cell transcriptomics to map how meningiomas evolve from primary to recurrent states
To address this gap, researchers from Korea University set out to map the evolutionary trajectory of meningiomas at single-cell resolution. Their goal was to investigate how tumour cells and their microenvironment evolve between primary and recurrent disease, and to identify the molecular drivers of recurrence.
The team analysed matched patient samples using single-nuclei RNA sequencing (snRNA-seq), which allowed profiling of both tumour cells and their surrounding microenvironment. To capture the dynamic progression of tumour cells, they applied RNA velocity and latent time analysis, tracking transcriptional changes as tumours transitioned to recurrence. Findings were further validated using external RNA-seq datasets and immunohistochemistry (IHC), strengthening the robustness of the results.
The study uncovered several key insights. Recurrent meningiomas exhibited markedly higher proliferative activity compared to their primary counterparts, which were enriched in cell cycle–related processes. Rather than progressing linearly, recurrent tumours diverged into multiple aggressive transcriptional trajectories. Most notably, the researchers identified COL6A3 as a central player driving these transitions.
This work significantly advances our understanding of how meningiomas progress from primary to recurrent states. It emphasises the need to address both tumour cell evolution and tumour–immune interactions when designing therapies.
Ultimately, targeting COL6A3 may provide a promising strategy to prevent recurrence and improve outcomes for patients with high-grade meningiomas.
References supplied.
https://medicine.korea.ac.kr/en/index.do
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