Correlation between IDH1 gene mutation status and survival of patients treated for recurrent glioma

Abstract

Somatic mutations in the isocitrate dehydrogenase 1 (IDH1) gene have been frequently found in low-grade glioma and secondary glioblastoma and are associated with a significantly younger age at diagnosis and a superior overall survival. We investigated the IDH1 gene mutation status by nested PCR and denaturing gradient gel electrophoresis (DGGE) on DNA extracted from archival tumor blocks of 63 glioma patients who were treated following recurrence with the epidermal growth factor receptor (EGFR)-targeted blocking monoclonal antibody cetuximab, or the vascular endothelial growth factor (receptor) (VEGF(R))-targeted agents sunitinib malate and bevacizumab. In our study population, IDH1 mutation was significantly correlated with a longer overall survival (OS) from the time of initial diagnosis. Patients with IDH1 mutation also had a superior OS from the time of recurrence when treated with sunitinib or bevacizumab but a worse OS when treated with cetuximab. Our observations support the hypothesis that IDH1 mutation may correlate with the benefit from VEGF(R)- versus EGFR-targeted therapy at the time of recurrence in glioma patients.