Expression of IDH1 Mutant Protein R132H and SDHB in Adult and Pediatric Gliomas

Abstract

Isocitrate dehydrogenase 1 (IDH1) and Succinate dehydrogenase (SDH) mutant tumors may have increased levels of hypoxia inducible factor (HIF), which leads to a tumoral pseudohypoxic profile. Increased HIF levels may promote tumor progression by the activation of numerous cellular processes including resistance to apoptosis, vascular remodeling and angiogenesis. A high frequency of IDH1 mutations has been detected in adult but not in pediatric gliomas. However, loss of SDH expression has not been investigated in gliomas. To further explore the profile and possible contribution of IDH1 and SDHB to glioma tumorigenesis, we investigated the expression of IDH1-R132 mutant and SDHB in a series of 94 histologically confirmed pediatric and adult gliomas. There were 13 diffuse intrinsic pontine gliomas and 81 adult gliomas: 10 lowgrade astrocytomas 8 oligodendrogliomas, 4 ependymomas and 59 glioblastomas (GBMs). Pediatric brain stem gliomas were negative for mutant IDH1 (0/13) and showed preserved SDHB expression (13/13). IDH1 mutant tumors included 6/10 astrocytomas, 5/8 oligodendrogliomas, 0/4 ependymomas and 13/59 GBMs. No adult or pediatric glioma exhibited loss of SDHB expression. IDH1 mutations are frequently present in low- and high-grade gliomas, but not in pediatric brain stem gliomas. It appears that IDH1, but not SDHB, contributes to HIF stabilization in adult gliomas. However, IDH1 or SDHB alterations do not appear to play a role in pediatric gliomagenesis.