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Clinical characteristics, molecular reclassification trajectories and DNA methylation patterns of long- and short-term survivors of WHO grade II and III glioma

  • 0Division of Oncology, Department of Medicine I, Medical University of Vienna, Waehringer Guertel 18-20, Vienna, Austria.
Journal of Neurology +

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February 15, 2025

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February 15, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Clinical outliers in diffuse gliomas exhibit distinct molecular profiles, impacting survival. Understanding these differences through molecular profiling is crucial for refining diagnoses and treatment strategies for long-term survivors (LTS) and short-term survivors (STS).

Area Of Science

  • Neuro-oncology
  • Molecular Pathology
  • Genomics

Background

  • Diffuse gliomas previously classified as "lower-grade" present heterogeneous prognoses, complicating clinical decision-making.
  • Identifying biological drivers of differential survival outcomes in these patients is essential.

Purpose Of The Study

  • To investigate the molecular profiles of clinical outliers among diffuse glioma patients.
  • To gain insights into the biological mechanisms distinguishing long-term survivors (LTS) from short-term survivors (STS).

Main Methods

  • Analysis of 385 patients (≥18 years) with diffuse glioma, WHO grade II/III.
  • Definition of STS (<1 year overall survival) and LTS (>10 years overall survival).
  • DNA methylation profiling using Illumina EPIC 850k platform.

Main Results

  • LTS (n=294) and STS (n=91) showed significant clinical differences (age, performance status, resection extent, symptoms).
  • Molecular reclassification revealed IDH-mutant gliomas in 95.5% of LTS versus 12.7% of STS.
  • DNA methylation identified two distinct clusters correlating with survival and IDH mutation status, with altered signaling pathways in rare subtypes.

Conclusions

  • Distinct clinical and molecular features differentiate LTS and STS in diffuse gliomas.
  • Extended molecular workup is critical for accurate diagnosis and prognostication.
  • Further characterization of rare subtypes is needed to optimize treatment and clinical trial design.

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