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

• Verfasst von: Vollmuth, Philipp [VerfasserIn]
• Verfasst von: Sahm, Felix [VerfasserIn]
• Verfasst von: Radbruch, Alexander [VerfasserIn]
• Verfasst von: Wick, Wolfgang [VerfasserIn]
• Verfasst von: Heiland, Sabine [VerfasserIn]
• Verfasst von: Deimling, Andreas von [VerfasserIn]
• Verfasst von: Bendszus, Martin [VerfasserIn]
• Verfasst von: Wiestler, Benedikt [VerfasserIn]
• Titel: IDH mutation status is associated with a distinct hypoxia/angiogenesis transcriptome signature which is non-invasively predictable with rCBV imaging in human glioma
• Verf.angabe: Philipp Kickingereder, Felix Sahm, Alexander Radbruch, Wolfgang Wick, Sabine Heiland, Andreas von Deimling, Martin Bendszus & Benedikt Wiestler
• E-Jahr: 2015
• Jahr: 05 November 2015
• Fussnoten: Gesehen am 29.06.2020
• Titel Quelle: Enthalten in: Scientific reports
• Ort Quelle: [London] : Macmillan Publishers Limited, part of Springer Nature, 2011
• Jahr Quelle: 2015
• Band/Heft Quelle: 5(2015) Artikel-Nummer 16238, 9 Seiten
• ISSN Quelle: 2045-2322
• DOI: doi:10.1038/srep16238
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1702884856

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.