Introduction
Materials and methods
Tumor samples, isolation of DNA, PCR, sequencing and mutation analysis
Glioblastoma patient data
IDH1 wt | IDH1 mutated | P value | ||
---|---|---|---|---|
Samples | 80 | 18 | ||
Tumor occurrence | Primary glioblastoma | 75 (95%) | 10 (56%) | <0.001 |
Secondary glioblastoma | 5 (5%) | 8 (44%) | ||
Age (years) | 58 (27–80) | 41 (28–62) | <0.001 | |
Gender | M | 44 (55%) | 9 (50%) | 0.704 |
F | 36 (45%) | 9 (50%) | ||
KPS | 75 (50–90) | 76 (50–90) | 0.813 | |
Surgical procedure | Biopsy or radical resection | 34 (43%) | 7 (39%) | 0.782 |
Gross total removal | 46 (57%) | 11(61%) | ||
Irradiation dosage (Gy) | 39 (0–78) | 48 (0–66) | 0.193 | |
Other therapy | No additional therapy | 53 (66%) | 8 (44%) | 0.086 |
Additional therapy | 27 (34%) | 10 (56%) |
Metabolic mapping
Image analysis
Statistical analysis
Univariate Cox regression | Multivariate Cox regression | |||||
---|---|---|---|---|---|---|
HR | 95% CI |
P
| HR | 95% CI |
P
| |
Age (per year) | 1.028 | 1.012–1.045 | 0.001 | 1.010 | 0.990–1.031 | 0.328 |
Sex | 1.114 | 0.728–1.799 | 0.559 | * | * | * |
KPS (per 10 points) | 0.969 | 0.949–0.989 | 0.002 | 0.974 | 0.954–0.995 | 0.018 |
Resection (gross total removal vs. biopsy or resection) | 0.628 | 0.402–0.980 | 0.040 | 0.807 | 0.508–1.282 | 0.364 |
Irradiation dosage, per Gy | 0.979 | 0.970–0.987 | <0.001 | 0.979 | 0.968–0.990 | <0.001 |
Other therapy (additional therapy vs. non-additional therapy) | 0.415 | 0.261–0.660 | <0.001 | 0.605 | 0.336–1.092 | 0.095 |
Secondary versus primary glioblastoma | 0.598 | 0.305–1.172 | 0.134 | * | * | * |
IDH1 mutated versus non-mutated | 0.273 | 1.137–0.543 | <0.001 | 0.209 | 0.093–0.471 | <0.001 |
Results
Mutational profiling of IDH1 and IDH2 in glioblastoma
Mutation at IDH1 R132 is an independent prognostic factor for improved survival in glioblastoma patients
IDH1 R132 mutations are associated with diminished in situ NADP+-dependent IDH activity in glioblastoma cells
Normal brain | Wild-type glioblastoma | IDH1-mutated glioblastoma | |
---|---|---|---|
IDH | 1.95 ± 1.17 | 3.82 ± 2.03 | 2.02 ± 1.73 |
G6PDH | 0.99 ± 0.16 | 1.59 ± 0.76 | 1.12 ± 0.74 |
6PGDH | 0.10 ± 0.05 | 0.23 ± 0.16 | 0.20 ± 0.10 |
MDH | 0.30 ± 0.12 | 0.19 ± 0.17 | 0.23 ± 0.20 |
H6PDH | 0.02 ± 0.01 | 0.09 ± 0.05 | 0.04 ± 0.02 |
Total capacity | 3.34 ± 1.12 | 5.88 ± 2.73 | 3.65 ± 2.29 |