Isocitrate dehydrogenase-1 mutations as prognostic biomarker in glioblastoma multiforme patients in West Bohemia

Abstract

Introduction: Glioblastoma multiforme (GBM) is the most malignant primary brain tumor in adults. Recent whole-genome studies revealed novel GBM prognostic biomarkers such as mutations in metabolic enzyme IDH-isocitrate dehydrogenases (IDH1 and IDH2). The distinctive mutation IDH1 R132H was uncovered to be a strong prognostic biomarker for glioma patients. We investigated the prognostic role of IDH1 R132H mutation in GBM patients in West Bohemia.

Methods: The IDH1 R132H mutation was assessed by the RT-PCR in the tumor samples from 45 GBM patients treated in the Faculty Hospital in Pilsen and was correlated with the progression free and overall survival.

Results: The IDH1 R132H mutation was identified in 20 from 44 GBM tumor samples (45.4%). The majority of mutated tumors were secondary GBMs (16 in 18, 89.9%). Low frequency of IDH1 mutations was observed in primary GBMs (4 in 26, 15.3%). Patients with IDH R132H mutation had longer PFS, 136 versus 51 days (P < 0.021, Wilcoxon), and OS, 270 versus 130 days (P < 0.024, Wilcoxon test).

Summary: The prognostic value of IDH1 R132H mutation in GBM patients was verified. Patients with mutation had significantly longer PFS and OS than patients with wild-type IDH1 and suffered more likely from secondary GBMs.

Figure 1

Progression-free survival of patients with glioblastoma with (red line) or without (blue line) IDH1 R132H gene mutation.

Figure 2

Overall survival of patients with glioblastoma with (red line) or without (blue line) IDH1 R132H gene mutation.

Figure 3

The representation of IDH1 mutations in various cancers [14].

Figure 4

The representation of IDH1 mutations in various types of central nervous system tumors [14].