The enzymatic activity of the proteins that were produced from normal and mutant IDH1 and IDH2 genes was determined in cultured glioma cells that were transfected with these genes.
We report on an inverse association of IDH1 and IDH2 mutations in these gliomas and a non-random distribution of the mutation types within the tumor entities.
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.
IDH1 mutations are a novel positive prognostic factor in anaplastic gliomas, with a favorable impact stronger than that of 1p/19q codeletion or MGMT promoter methylation.
The assay detected IDH mutations in biopsy material containing mostly glioma and in concomitant near-miss stereotactic core biopsies that were otherwise equivocal for the presence of glioma by light microscopy.
IDH1 and IDH2 mutations define a specific subtype of gliomas and may have significant utility for the diagnosis, prognosis, and treatment of patients with these tumors.
Somatic mutations in the isocitrate dehydrogenase 1 gene (IDH1) occur at high frequency in gliomas and seem to be a prognostic factor for survival in glioblastoma patients.
Our results suggest that in pediatric high-grade gliomas: (i) histological grading does not have strong prognostic significance, (ii) YKL-40 overexpression is less frequent than adult high-grade gliomas and does not correlate with a more aggressive behavior, (iii) TP53 mutations but not p53 expression may correlate with a more aggressive behavior, and (iv) IDH1 mutations are absent.
Our data also confirm the prognostic impact of IDH1/IDH2 mutation in gliomas whatever grade considered: patients harboring mutations of IDH1/IDH2 have an improved median overall survival.
The most frequent IDH1 mutation found in the majority of WHO grade II and III gliomas can be visualized with an antibody specifically detecting mutant IDH1 protein.
Mutations in the IDH1 gene at position R132 coding for the enzyme cytosolic isocitrate dehydrogenase are known in glioma and have recently been detected also in acute myeloid leukemia (AML).