Isocitrate Dehydrogenase 1 Codon 132 Mutation Is an Important Prognostic Biomarker in Gliomas

Purpose Unexpected mutations affecting the isocitrate dehydrogenase (IDH1) gene at codon 132 have been found in 12% of glioblastomas. Patients and Methods IDH1 codon 132 sequencing was performed in a series of 404 patients with glioma (100 grade 2, 121 grade 3, and 183 grade 4 gliomas) and correlated with histology, genomic profile, methylguanyl methyltransferase (MGMT) promoter methylation status, and outcome. Results A total of 155 codon 132 mutations were found, of which 131 were Arg132His (88.5%). The IDH1 mutation was inversely correlated with grade, affecting 77% of grade 2, 55% of grade 3, and 6% of grade 4 gliomas (P 10 15 ). The IDH1 mutation was tightly associated with a 1p19q codeleted genotype (P 10 14 ) and an MGMT methylated status (P .001) but mutually exclusive with EGFR amplification (P 10 15 ) and loss of chromosome 10 (P 10 15 ). The presence (v absence) of IDH1 mutation was associated with a better outcome in grade 2 (150.9 v 60.1 months, respectively; P .01), grade 3 (81.1 v 19.4 months, respectively; P .001), and grade 4 gliomas (27.4 v 14 months, respectively; P .01). After adjustment for grade, age, MGMT status, genomic profile, and treatment, multivariate analysis confirmed that IDH1 mutation was an independent favorable prognostic marker (hazard ratio 0.297; 95% CI, 0.157 to 0.564, P .00021).