The impact of adjuvant radiotherapy on molecular prognostic markers in gliomas

PURPOSE: Changes in MGMT promoter methylation, IDH1 and IDH2 mutation, and 1p/19q co-deletion status in gliomas between first and subsequent resections and their associated clinical factors are poorly described. In this study, we assayed these biomarkers in the clinical setting. PATIENTS AND METHODS: We used multiplex ligation-dependent probe amplification to measure MGMT promoter methylation, IDH mutation status, and 1p/19q co-deletion in 45 paired tumor samples from patients undergoing resection and subsequent re-resections for gliomas. RESULTS: Molecular changes were present in 20 patients (44%). At least one molecular characteristic changed over time in 89% of patients with primary grade III tumors. Gliomas with IDH wild-type and/or non-co-deleted were stable, but IDH1/2 mutation and/or co-deletion were sometimes lost at the time of recurrence. In a multivariate analysis, adjuvant radiotherapy alone was independently associated (P=0.02) with changes in molecular profile. CONCLUSION: Molecular biomarkers change in gliomas during the course of the disease, most often MGMT methylation status. These changes in genetic profiles are related to adjuvant treatment with radiotherapy alone, which might be important for individualized treatment planning over the disease course.