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

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

Author information

1
Department of Neuroradiology, University of Heidelberg Medical Center, Heidelberg, Germany.
2
Department of Neuropathology, University of Heidelberg Medical Center, Heidelberg, Germany.
3
German Cancer Consortium (DKTK), Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
4
DKFZ, Department of Radiology, Heidelberg, Germany.
5
Neurology Clinic, University of Heidelberg Medical Center, Heidelberg, Germany.
6
DKTK, Clinical Cooperation Unit Neurooncology, DKFZ, Heidelberg, Germany.

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.

PMID:
26538165
PMCID:
PMC4633672
DOI:
10.1038/srep16238
[Indexed for MEDLINE]
Free PMC Article

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