Article
Impact of genome-wide DNA methylation profiling on intensity of 5-ALA fluorescence-guided resection of IDH-wild type glioblastoma
Einfluss der DNA-Methylierungsmuster auf die Intensität der 5-ALA Fluoreszenz-gestützten Resektion bei IDH-Wildtyp Glioblastomen
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Authors
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Richard Drexler
- Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Neurochirurgie, Hamburg, Deutschland
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Thomas Sauvigny
- Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Neurochirurgie, Hamburg, Deutschland
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Manfred Westphal
- Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Neurochirurgie, Hamburg, Deutschland
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Ulrich Schüller
- Universitätsklinikum Hamburg-Eppendorf, Institut für Neuropathologie, Hamburg, Deutschland
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Lasse Dührsen
- Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Neurochirurgie, Hamburg, Deutschland
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Franz Lennard Ricklefs
- Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Neurochirurgie, Hamburg, Deutschland
| Published: | May 25, 2022 |
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Outline
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Objective: 5-aminolevulinic acid (5-ALA) fluorescence-guided resection was proven to increase the percentage of complete resections of CNS tumours and improves the PFS of IDH-wild type glioblastoma. Even though 5-ALA-guided tumor resection of high-grade gliomas is the current state of the art, reports about a missing 5-ALA fluorescence exist. A sufficient explanation for these challenging cases is missing. In this study, we aimed to investigate the influence of methylation subclasses and genetic alterations using genome-wide DNA methylation on the 5-ALA-fluorescence intensity in IDH-wild type glioblastoma.
Methods: Patients who were newly diagnosed with IDH-wild type glioblastoma after 18 years of age and underwent surgery were retrospectively analysed from our prospective maintained database. The intensity of intraoperative 5-ALA fluorescence was categorized as no visible, intermediate, or strong fluorescence assessed from the operating neurosurgeon. DNA was extracted from tumors and analyzed for genome-wide DNA methylation patterns using the Illumina EPIC (850k) array. Assessment of gene alteration was performed using the brain tumor classifier of the DKFZ.
Results: 74 patients were included in this study. Of these, 12 patients (16.2%) showed no 5-ALA fluorescence whereas 43 patients (59.7%) had an intermediate and 19 patients (24.1%) a strong intensity. Basic characteristics were balanced between these groups (p>0.05). The 5-ALA fluorescence intensity was not influenced by DNA methylation subgroups (RTK I, RTK II and mesenchmal). However, an EGFR amplification was found to be associated with the intensity of intraoperative 5-ALA (p<0.01). All glioblastomas with a missing 5-ALA fluorescence, were EGFR-amplified using the copy number variation (CNV)-profile, respectively. In addition, MGMT promotor methylation status and PDGFRAamplification correlated significant with a stronger intensity (p<0.01).
Conclusion: Our study demonstrates the association between the intensity of 5-ALA fluorescence of IDH-wild type glioblastoma and EGFR gene amplification but not DNA methylation subclasses. Our results demonstrate this correlation in vivo for the first time.
