Recently identified mutations in IDH1/IDH2, however, are specific for diffuse gliomas, occur frequently in grade II/III gliomas and are of prognostic value in grade III gliomas, as well in glioblastomas in which they characterize secondary glioblastomas.
The total NADPH production capacity in glioblastoma was provided for 65% by IDH activity and the occurrence of IDH1 (R132 ) mutation reduced this capacity by 38%.
By direct genomic DNA sequencing, we analyzed exon 4 of the IDH1 and IDH2 genes that harbored the mutation hot spots codon 132 and 172 of the two genes in glioblastoma, respectively, in 12 thyroid cancer cell lines, 20 FTC, and 18 ATC tumor samples.
As IDH mutations are not characteristic of grade IV primary glioblastomas, this antibody cannot differentiate primary glioblastoma from reactive gliosis.
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.
Some findings, such as that of IDH mutation in low-grade gliomas and secondary glioblastoma (GBM), fit well into established notions of different routes of gliomagenesis.
IDH activity was the main provider of NADPH in human normal brain and glioblastoma, but its role was modest in NADPH production in rodent brain and other tissues.
Currently, three molecular markers, related to better outcome, are particularly useful and complement the histological classification: the 1p/19q codeletion strongly predicts prolonged response to treatment and prolonged survival in oligodendroglial tumors; the O(6)-methylguanine-DNA methyltransferase promoter methylation, which is hypothesized to render the cell more vulnerable to alkylants, is associated with a stronger benefit of concomitant chemoradiotherapy in glioblastomas; mutations of the IDH1 (more rarely IDH2) gene affects 40% of gliomas (but 100% of the 1p/19q codeleted gliomas) and is inversely correlated to grade.
IDH mutations were frequent in oligodendroglial tumors (37/52, 71%) and diffuse astrocytomas (17/29, 59%), and were less frequent in anaplastic astrocytomas (8/29, 28%) and glioblastomas (13/125, 10%).
In spite of a recent surge in elucidating the tumorigenic activity of IDH mutations in glioblastoma, the underlying biological mechanisms remain poorly understood.
The isocitrate dehydrogenase 1 (IDH1) or 2 (IDH2) genes are mutated in 50-80% of astrocytomas, oligodendrogliomas or oligoastrocytomas of grades II and III, and secondary glioblastomas; they are, however, seldom mutated in primary glioblastomas and never in other types of glioma.
Mutations in the IDH1 and IDH2 genes encoding isocitrate dehydrogenases are frequently found in human glioblastomas and cytogenetically normal acute myeloid leukaemias (AML).
Somatic mutations of the isocitrate dehydrogenase (IDH) genes occur frequently in WHO grades II and III gliomas and WHO grade IV secondary glioblastomas.
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.
The presented approach is applicable for prospective validation and appears promising towards an effective glioblastoma patient stratification in addition to IDH mutations.
Mutations in isocitrate dehydrogenase -1 or -2 (IDH1 or IDH2) are found in the majority of WHO grade II and III diffuse gliomas and secondary glioblastomas.
IDH1 and IDH2 are mutated in 50%-80% of astrocytomas, oligodendrogliomas, oligoastrocytomas, and secondary glioblastomas but are seldom mutated in primary glioblastomas.
The IDH mutations were frequent in WHO grade II and III glioma (59.5%) and secondary glioblastomas (63.4%) and were less frequent in primary glioblastomas (7.13%).
We retrospectively evaluated the incidence of PP in adult patients with sGBM treated with chemoradiation therapy (CRTx) using temozolomide (TMZ) and sought to assess if there was an association between PP and MGMT promoter methylation status, IDH mutations status, or 1p/19q codeletion.
Recent genome wide sequencing has identified mutations in IDH1/IDH2 predominantly in grade II-III gliomas and secondary glioblastomas which are associated with favorable clinical outcome.