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

Sci Rep. 2015 Nov 5;5:16238. doi: 10.1038/srep16238.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers, Tumor / genetics
  • Brain / pathology
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / pathology
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / pathology
  • Female
  • Glioma / genetics*
  • Glioma / pathology
  • Humans
  • Hypoxia / genetics*
  • Hypoxia / pathology
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Isocitrate Dehydrogenase / genetics*
  • Magnetic Resonance Imaging / methods
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Neovascularization, Pathologic / genetics*
  • Neovascularization, Pathologic / pathology
  • Transcriptome / genetics*
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Isocitrate Dehydrogenase