<i>EGFR</i> Amplification Is a Phenomenon of <i>IDH</i> Wildtype and <i>TERT</i> Mutated High-Grade Glioma: An Integrated Analysis Using Fluorescence In Situ Hybridization and DNA Methylome Profiling
Dorothee Hölzl,
Georg Hutarew,
Barbara Zellinger,
Beate Alinger-Scharinger,
Hans U. Schlicker,
Christoph Schwartz,
Karl Sotlar,
Theo F. J. Kraus
Affiliations
Dorothee Hölzl
Institute of Pathology, University Hospital Salzburg, Paracelsus Medical University, Müllner Hauptstr. 48, A-5020 Salzburg, Austria
Georg Hutarew
Institute of Pathology, University Hospital Salzburg, Paracelsus Medical University, Müllner Hauptstr. 48, A-5020 Salzburg, Austria
Barbara Zellinger
Institute of Pathology, University Hospital Salzburg, Paracelsus Medical University, Müllner Hauptstr. 48, A-5020 Salzburg, Austria
Beate Alinger-Scharinger
Institute of Pathology, University Hospital Salzburg, Paracelsus Medical University, Müllner Hauptstr. 48, A-5020 Salzburg, Austria
Hans U. Schlicker
Institute of Pathology, University Hospital Salzburg, Paracelsus Medical University, Müllner Hauptstr. 48, A-5020 Salzburg, Austria
Christoph Schwartz
Department of Neurosurgery, University Hospital Salzburg, Paracelsus Medical University, Ignaz-Harrer-Str. 79, A-5020 Salzburg, Austria
Karl Sotlar
Institute of Pathology, University Hospital Salzburg, Paracelsus Medical University, Müllner Hauptstr. 48, A-5020 Salzburg, Austria
Theo F. J. Kraus
Institute of Pathology, University Hospital Salzburg, Paracelsus Medical University, Müllner Hauptstr. 48, A-5020 Salzburg, Austria
Gliomas are the most common intrinsic brain tumors in adults, and in accordance with their clinical behavior and patients’ outcome, they are graded by the World Health Organization (WHO) classification of brain tumors. One very interesting candidate for targeted tumor therapy may be epidermal growth factor receptor (EGFR) amplification. Here, we performed an integrated comparative analysis of EGFR amplification in 34 glioma samples using standard fluorescence in situ hybridization (FISH) and Illumina EPIC Infinium Methylation Bead Chip and correlated results with molecular glioma hallmarks. We found that the EPIC analysis showed the same power of detecting EGFR amplification compared with FISH. EGFR amplification was detectable in high-grade gliomas (25%). Moreover, EGFR amplification was found to be present solely in IDH wildtype gliomas (26%) and TERT mutated gliomas (27%), occurring independently of MGMT promoter methylation status and being mutually exclusive with 1p/19q codeletion (LOH). In summary, EPIC Bead Chip analysis is a reliable tool for detecting EGFR amplification and is comparable with the standard method FISH. EGFR amplification is a phenomenon of IDH wildtype TERT mutated high-grade gliomas.
