a dysregulated GSK3b/EZH2 axis in the progression of NPC, which might hold significant promise for identifying critical molecular targets and improving NPC therapy. Gliomas, which are the most common primary intracranial tumours, are classified as grade I to grade IV, according to the 2007 WHO Classification of Tumours of the Central Nervous System. Despite advances in diagnostic and therapeutic techniques, the prognosis for most glioma patients remains dismal. Histomorphological criteria alone are not sufficient to predict the clinical outcome of gliomas. Thus, new avenues must be taken to integrate the molecular advances with the histological assessment of gliomas. Recently, the sequencing of human gliomas has identified mutations in the isocitrate dehydrogenase 1 and 2 genes. IDH mutations are relatively glioma-specific. However, IDH1 and IDH2 mutations are also found in acute myeloid leukaemia. The IDH gene mutations are found frequently in malignant gliomas and are likely to be involved in the early stage of gliomagenesis, even before TP53 mutations or loss of 1p and 19q. The IDH1 mutations occur in the highly conserved residue R132, which is in the catalytic domain, where it binds to its substrate. The mutations in IDH2 consistently occur at the analogous amino acid R172, which is functionally equivalent to amino acid 132 of IDH1. IDH1 mutations have been found in approximately 80 of grades II-III gliomas and secondary glioblastomas but have been found in less than 10 of primary glioblastomas. The IDH2 mutations have also been described in gliomas, although at a lower 1187187-10-5 frequency. The IDH1 and IDH2 enzymes catalyse oxidative decarboxylation of isocitrate into a-ketoglutarate, thereby reducing NADP to NADPH. The tumourigenic potential of a mutant IDH protein is under intense 1194506-26-7 investigation. First, a heterozygous point mutation in codon 132 impairs the interaction of the enzyme with isocitrate both sterically and electrostatically, and the mutant IDH1 molecules dominantly inhibit the activity of wild-type IDH1 by forming a catalytically inactive heterodimer. Second, the mutations cause reduced formation of aKG and decreased cytoplasmic levels of aKG incre
