Somatic mutations in IDH1 and IDH2 genes in gliomas

Primary brain tumors account for about 2 % of all adult malignancies. The incidence of primary brain tumors has nearby doubled within the past 30 years and was 7.95 per 100 000 inhabitants in the Czech Republic (in 2010). The most common brain tumors are gliomas and meningiomas. Gliomas include tumors of various types and grades.

IDH1 and IDH2 genes are coding isocitrate dehydrogenases, which are members of isocitrate dehydrogenase family, catalysing the oxidative decarboxylation of isocitrate to α-ketoglutarate, resulting in the production of NADPH.

Mutations in IDH1 and IDH2 genes are frequent in low-grade astrocytic and oligodendroglial tumors and in secondary glioblastomas. IDH mutations are rare or absent in other types of glial tumors, such as pilocytic astrocytomas and ependymomas. These mutations are associated with more favourable prognosis and prolonged overall survival in glioblastoma patients. IDH1 mutations are located in codon 132 with the most frequent R132H mutation, which was observed in 83–91 % of all mutations.

Mutations in IDH2 gene are rare and occur almost exclusively in codon 172. In our study mutation R132H in IDH1 gene was determined by immunohistochemistry with IDH1 R132H Mouse anti Human unconj. antibody (Dianova GmbH) and further investigated for presence of mutations in IDH1 and IDH2 genes in glioma patiens by molecular genetic methods (SNaPshot assay, sequencing analysis). Determination of IDH1/2 mutations has prognostic and diagnostic value and can contribute to the exact differentiation between histological types of gliomas.