Somatic mutations in the IDH1 gene encoding cytosolic
NADP+-dependent
isocitrate dehydrogenase have been shown in the majority of
astrocytomas,
oligodendrogliomas and oligoastrocytomas of WHO grades II and III. IDH2 encoding mitochondrial
NADP+-dependent
isocitrate dehydrogenase is also mutated in these
tumors, albeit at much lower frequencies. Preliminary data suggest an importance of IDH1 mutation for prognosis showing that patients with
anaplastic astrocytomas,
oligodendrogliomas and oligoastrocytomas harboring IDH1 mutations seem to fare much better than patients without this mutation in their
tumors. To determine mutation types and their frequencies, we examined 1,010 diffuse
gliomas. We detected 716 IDH1 mutations and 31 IDH2 mutations. We found 165 IDH1 (72.7%) and 2 IDH2 mutations (0.9%) in 227 diffuse
astrocytomas WHO grade II, 146 IDH1 (64.0%) and 2 IDH2 mutations (0.9%) in 228
anaplastic astrocytomas WHO grade III, 105 IDH1 (82.0%) and 6 IDH2 mutations (4.7%) in 128
oligodendrogliomas WHO grade II, 121 IDH1 (69.5%) and 9 IDH2 mutations (5.2%) in 174
anaplastic oligodendrogliomas WHO grade III, 62 IDH1 (81.6%) and 1 IDH2 mutations (1.3%) in 76 oligoastrocytomas WHO grade II and 117 IDH1 (66.1%) and 11 IDH2 mutations (6.2%) in 177 anaplastic oligoastrocytomas WHO grade III. 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 mutations of the R132C type are strongly associated with
astrocytoma, while IDH2 mutations predominantly occur in oligodendroglial
tumors. In addition, patients with anaplastic
glioma harboring IDH1 mutations were on average 6 years younger than those without these alterations.