title: IDH mutation status is associated with a distinct hypoxia/angiogenesis transcriptome signature which is non-invasively predictable with rCBV imaging in human glioma.
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.
authors.affiliation: Department of Neuroradiology, University of Heidelberg Medical Center, Heidelberg, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Kickingereder
authors.affiliation: Department of Neuropathology, University of Heidelberg Medical Center, Heidelberg, Germany.|German Cancer Consortium (DKTK), Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Sahm
authors.affiliation: Department of Neuroradiology, University of Heidelberg Medical Center, Heidelberg, Germany.|DKFZ, Department of Radiology, Heidelberg, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Radbruch
authors.affiliation: Neurology Clinic, University of Heidelberg Medical Center, Heidelberg, Germany.|DKTK, Clinical Cooperation Unit Neurooncology, DKFZ, Heidelberg, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wick
authors.affiliation: Department of Neuroradiology, University of Heidelberg Medical Center, Heidelberg, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Heiland
authors.affiliation: Department of Neuropathology, University of Heidelberg Medical Center, Heidelberg, Germany.|German Cancer Consortium (DKTK), Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Andreas von
authors.initials: Av
authors.lastname: Deimling
authors.affiliation: Department of Neuroradiology, University of Heidelberg Medical Center, Heidelberg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Bendszus
authors.affiliation: Department of Neuroradiology, University of Heidelberg Medical Center, Heidelberg, Germany.|Neurology Clinic, University of Heidelberg Medical Center, Heidelberg, Germany.|DKTK, Clinical Cooperation Unit Neurooncology, DKFZ, Heidelberg, Germany.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Wiestler
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics; D001921:Brain / Q000473:pathology; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D005260:Female; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D000860:Hypoxia / Q000235:genetics* / Q000473:pathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000473:pathology; D059467:Transcriptome / Q000235:genetics*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007521:Isocitrate Dehydrogenase