R132H mutation in IDH1 gene is associated with increased tumor HIF1-alpha and serum VEGF levels in primary glioblastoma multiforme

PubMed ID: 28667042Goals. Glioblastoma multiforme (GBM) is the most common form of primary brain tumors. Although mutations in isocitrate dehydrogenase-1 (IDH1) have been identified in a number of cancers, their role in tumor development has not been fully elucidated. In this study, we aimed to investigate the association between IDH1 mutations, tumor tissue HIF-1 alpha, and serum VEGF levels in patients with primary GBM for the first time. Methods. 32 patients (mean age, years: 58±14.0) diagnosed with primary glioblastoma multiforme were screened for IDH1 mutations (R132H, R132S, R132C and R132L) by direct sequencing. Serum VEGF and tumor tissue HIF1-alpha levels were measured by enzyme-linked immunosorbent assay. Associations between categoric variables were determined using chi-square tests. Differences between two groups were compared with t test for continuous variables. Results. Six percent of patients were found to be heterozygous for R132H mutation. Tumor HIF1-alpha and serum VEGF levels were found to be significantly increased in IDH1-mutated tumor tissues (p < 0.0001 and p=0.0454, respectively). Conclusion. Our results suggest that mutated IDH1 may contribute to carcinogenesis via induction of HIF-1 alpha pathway in primary GBM. © 2017 by the Association of Clinical Scientists, Inc