The expression levels of LOX, BMP1 and HIF1A were correlated and analyzed according to IDH1 mutation status and to the clinical end-point of overall survival of glioblastoma patients.
The discovery of somatic mutations in the isocitrate dehydrogenase (IDH) enzymes through a genome-wide mutational analysis in glioblastoma represents a milestone event in cancer biology.
Staining of mutant IDH1 was positive in nine neoplastic lesions (3 diffuse astrocytomas, 2 anaplastic astrocytomas, and 1 oligodendroglioma, oligoastrocytoma, anaplastic oligodendroglioma, and glioblastoma); it was negative in all ten non-neoplastic lesions.
Furthermore, SMab-1 specifically stained the IDH1-R132S-expressing glioblastoma cells in immunocytochemistry and immunohistochemistry, but did not react with IDH1-WT or IDH1-R132H-containing glioblastoma cells.
The presented approach is applicable for prospective validation and appears promising towards an effective glioblastoma patient stratification in addition to IDH mutations.
We investigated the prognostic significance of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and TP53 mutation status dependent on isocitrate dehydrogenase 1 (IDH1) mutation in glioblastoma patients.
Overexpression of IDH1(R132H) and IDH2(R172K) mutant protein in glioblastoma cells resulted in increased radiation sensitivity and altered ROS metabolism and suppression of growth and migration in vitro.
Continuous administration of DS-1001b impaired tumor growth and decreased 2-HG levels in subcutaneous and intracranial xenograft models derived from a glioblastoma patient with IDH1 mutation.
MATH values were increased in patients with glioma with the wild-type isocitrate dehydrogenase (NADP<sup>(+)</sup>) (IDH)1/2 (IDH-wt) gene (P=0.001) and glioblastoma (GBM; P=0.001).
Patients with IDH1/2 wild-type gliomas and glioblastoma-like genomic alterations, including gain on chromosome arm 7q (+7q), loss on chromosome arm 10q (-10q), TERT promoter mutation and oncogene amplification, displayed the worst outcome.
Widely metastatic IDH1-mutant glioblastoma with oligodendroglial features and atypical molecular findings: a case report and review of current challenges in molecular diagnostics.
We identified a small cohort of WHO grade II-III astrocytomas that harbored the IDH1R132H mutation, as confirmed by both immunohistochemistry and molecular sequence analysis, which nonetheless had unexpectedly rapid recurrence and subsequent progression to glioblastoma.
Recent DNA methylation analyses revealed a small group of IDH mutant diffuse gliomas exhibiting decreased DNA hypermethylation resulting in substantial unfavorable prognosis comparable to glioblastoma.
Another mitochondrial and TCA cycle-related protein, isocitrate dehydrogenase 2 is, together with IDH1, frequently mutated in the brain tumour glioblastoma.
1p/19q codeletion and IDH1 mutations are also useful to support and extend the histological classification of gliomas since they are strongly linked to oligodendroglial morphology and grade II/III gliomas, as opposed to glioblastoma, respectively.
Triple-positive (IDH1 and TERT mutation with 1p19q codeletion) glioma tended to be oligodendroglioma present with much better clinical outcome compared to TERT mutation only group who is glioblastoma inclined (median overall survival 39 months VS 18 months).
ATRX and IDH1-R132H immunohistochemistry with subsequent copy number analysis and IDH sequencing as a basis for an "integrated" diagnostic approach for adult astrocytoma, oligodendroglioma and glioblastoma.
Complete 1p/19q co-deletion, MGMT promoter methylation and/or IDH1 mutation generally signified a better prognosis for patients with a diffuse glioma including glioblastoma.
Glioblastoma can occur either de novo or by the transformation of a low grade tumour; the majority of which harbor a mutation in isocitrate dehydrogenase (IDH1).