# Epigenetic Characteristics in Primary and Recurrent Glioblastoma—Influence on the Clinical Course

## TL;DR

This study shows that epigenetic markers in glioblastoma tumors can change over time, which may affect their usefulness in predicting patient outcomes.

## Contribution

The study demonstrates that epigenetic markers like MGMT, p15, p16, and miRNAs can be unstable during glioblastoma progression, impacting their prognostic reliability.

## Key findings

- MGMT methylation changed in 30% of patients between primary and recurrent tumors.
- Patients with decreased miRNA-21 expression in recurrence had significantly longer survival.
- TCGA dataset confirmed similar instability in epigenetic markers.

## Abstract

Objective: Epigenetic tumor characteristics are in focus for glioblastoma prognosis. This raises the question if these characteristics present with stable expression during the progression of the disease, and if potential temporal instability might influence their prognostic value. Methods: A total of 44 patients suffering from glioblastoma who were treated for their primary and relapse tumors were included in the study. Tumor specimens from the initial and recurrent tumor resection were subjected to evaluation of MGMT, p15, and p16 methylation statuses. MiRNA-21, -24, -26a, and -181d expression was evaluated as well. The stability of these epigenetic markers during the progression of the disease was correlated with further clinical data. A Cancer Genome Atlas (TCGA) dataset of 224 glioblastoma patients was used as an independent cohort to validate the results. Results: Instability was observed in all examined epigenetic markers. MGMT methylation changed in 30% of patients, p15 methylation changed in 35%, and p16 methylation changed in 37.5% of cases. MiRNA expression in corresponding initial and relapse tumor specimens varied considerably in general, individual cases presented with a stable expression. Patients with a decreased expression of miRNA-21 in their recurrence tumor showed significantly longer overall survival. These results are supported by the data from TCGA indicating similar results. Conclusions: Epigenetic characteristics may change during the course of glioblastoma disease. This may influence the prognostic value of derived molecular markers.