IDH mutation status is associated with a distinct hypoxia/angiogenesis transcriptome signature which is non-invasively predictable with rCBV imaging in human glioma
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...
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| Main Authors: | , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
05 November 2015
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| In: |
Scientific reports
Year: 2015, Volume: 5, Issue: 1 |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep16238 |
| Online Access: | Resolving-System, lizenzpflichtig, Volltext: https://doi.org/10.1038/srep16238 Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/srep16238 
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| Author Notes: | Philipp Kickingereder, Felix Sahm, Alexander Radbruch, Wolfgang Wick, Sabine Heiland, Andreas von Deimling, Martin Bendszus & Benedikt Wiestler |
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| 520 | |a 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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