Transgenic mouse models of Idh-mutated neural stem cells: an appropriate model for low grade glioma?

The large majority of diffuse gliomas, classified by World Health Organization (WHO) guidelines as grade II and III, and the grade IV gliomas that have progressed from these lower grade cancers (the so-called secondary glioblastomas) carry heterozygous hotspot mutations in IDH1 or IDH2, the genes encoding the metabolic enzymes isocitrate dehydrogenase 1 (IDH1, cytosolic/peroxisomal) or IDH2 (the mitochondrial variant) (1,2). Besides glioma, the occurrence of these mutations is limited to a small number of cancer types, including acute myeloid leukemia (AML), enchondromas, chondrosarcoma and hepatic cholangiocarcinoma (3).