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The recent identification of  IDH  mutations in gliomas and several other cancers suggests that this pathway is involved in oncogenesis; however effector functions are complex and yet incompletely understood. To study the regulatory effects of  IDH  on  hypoxia-inducible-factor 1-alpha  ( HIF1A ), a driving force in hypoxia-initiated angiogenesis, we analyzed mRNA expression profiles of 288 glioma patients and show decreased expression of  HIF1A  targets on a single-gene and pathway level, strong inhibition of upstream regulators such as  HIF1A  and downstream biological functions such as angio- and vasculogenesis in  IDH  mutant tumors. Genotype/imaging phenotype correlation analysis with relative cerebral blood volume (rCBV) MRI – a robust and non-invasive estimate of tumor angiogenesis – in 73 treatment-naive patients with low-grade and anaplastic gliomas showed that a one-unit increase in rCBV corresponded to a two-third decrease in the odds for an  IDH  mutation and correctly predicted  IDH  mutation status in 88% of patients. Together, these findings (1) show that  IDH  mutation status is associated with a distinct angiogenesis transcriptome signature which is non-invasively predictable with rCBV imaging and (2) highlight the potential future of radiogenomics (i.e. the correlation between cancer imaging and genomic features) towards a more accurate diagnostic workup of brain tumors.

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IDH mutation status is associated with a distinct hypoxia/angiogenesis transcriptome signature which is non-invasively predictable with rCBV imaging in human glioma