A patient with two gliomas with independent oligodendroglioma and glioblastoma biology proved by DNA-methylation profiling: a case report and review of the literature

Kraus, Theo; Schwartz, Christoph; Machegger, Lukas; Zellinger, Barbara; Hölzl, Dorothee; Schlicker, H.; Pöppe, Johannes; Ladisich, Barbara; Spendel, Mathias; Kral, Michael; Sotlar, Karl

doi:10.1007/s10014-021-00423-0

Cited by 5 publications

(8 citation statements)

References 11 publications

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“…The lambda tumor-induced group, plain GQD treated, GQD-BSA conjugate treated, and GQD-Trastuzumab conjugate treated groups showed disturbed and altered cell bodies with extracellular space, scar formation, and hippocampal gliosis. While the GQD-Caspase 8 conjugate-treated group showed recuperate changes in damaged cell structures, reduced inflammation, and neurodegeneration [71,72].…”

Section: Histopathological Evaluation Of Gqd-treated Brain Tumor-indu...mentioning

confidence: 92%

Anti-cancer and neuroprotective effects of conjugated graphene quantum dot in brain tumor-bearing rat model

Patel,

Shah

2023

Nano Ex.

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Glioblastoma has been recognized as a most complex and highly malignant type of primary brain tumor. The rapid progression brain tumor model was developed by direct intracranial administration of ENU at the different focal brain points in the rat brains. The GQD was synthesized by bottom-up technique and functionalized with Trastuzumab and Caspase-8 antibody by Carbodiimide-amidation activation. The in-vitro cytotoxicity MTT assay was performed with all the GQD conjugates in SK-N-SH and N2a cell lines. The acute and chronic toxicity of synthesized GQD was performed in healthy rats and evaluated the hemolytic activity and CRP levels. A synthesized quasi-spherical 2D tiny GQD has a particle size of less than 10 nm and a 12.7% quantum yield. DSL, TEM, AFM, FTIR, and fluorescence spectroscopy characterized the GQD conjugates. In-silico molecular docking was a conformed static interaction between GQD and antibodies. GQD-conjugates showed dose-dependent toxicity in both cell lines and mild acute toxicity in rat blood. The GBM tumor-bearing rats were assessed for the anticancer and neuroprotective activity of the GQD conjugates. Histopathology, immunohistochemistry, metabolic, and inflammatory tumor biomarker estimation showed that the GQD_Caspase-8 conjugate showed better anti-tumor and neuroprotective effects than other conjugates.

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Section: Histopathological Evaluation Of Gqd-treated Brain Tumor-indu...mentioning

confidence: 92%

Anti-cancer and neuroprotective effects of conjugated graphene quantum dot in brain tumor-bearing rat model

Patel,

Shah

2023

Nano Ex.

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“…Molecular genetic analyses for IDH1 , IDH2 mutations, as well as DNA methylation were performed as previously described [ 26 , 27 , 28 ]. In brief, representative tumor regions were microscopically identified and dissected.…”

Section: Methodsmentioning

confidence: 99%

“…Mutational analysis of IDH1 and IDH2 genes was performed with either the AmpliSeq for Illumina Cancer Hotspot Panel v2 (Illumina, San Diego, CA, USA) or the AmpliSeq for Illumina Focus Panel (Illumina), respectively. Next generation sequencing was performed on an Illumina MiniSeq device following the manufacturer’s protocol [ 26 , 27 , 28 ].…”

Section: Methodsmentioning

confidence: 99%

“…Telomerase reverse transcriptase mutation analysis and MGMT methylation analysis were performed as described previously [ 26 , 27 , 28 ].…”

Section: Methodsmentioning

confidence: 99%

“…Methylation analysis was performed using the Infinium Methylation EPIC Bead Chip (Illumina) protocol [ 26 , 27 , 28 ]. Raw data files (idat-files) were analyzed using the molecularneuropathology.org bioinformatics pipeline of the German Cancer Research Center (DKFZ) and the v11b4 brain tumor classifier [ 29 ].…”

Section: Methodsmentioning

confidence: 99%

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Methylome Profiling of PD-L1-Expressing Glioblastomas Shows Enrichment of Post-Transcriptional and RNA-Associated Gene Regulation

Hutarew

Hölzl

Schiefer

et al. 2022

Cancers

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Glioblastomas are the most frequent primary brain tumors in adults. They show highly malignant behavior and devastating outcomes. Since there are still no targeted therapies available, median survival remains in the range of 12 to 15 months for glioblastoma patients. Programmed Cell Death Ligand 1 (PD-L1) is a promising novel candidate in precision medicine. Here, we performed integrated epigenome-wide methylation profiling of 866,895 methylation-specific sites in 20 glioblastoma samples comparing PD-L1 high- (i.e., TPS (tumor proportion score) > 30%) and PD-L1 low-expressing glioblastomas (i.e., TPS < 10%). We found 12,597 significantly differentially methylated CpGs (DMCG) (Δβ ≥ 0.1 and p-value < 0.05) in PD-L1 high- compared with PD-L1 low-expressing glioblastomas. These DMCGs were annotated to 2546 tiling regions, 139 promoters, 107 genes, and 107 CpG islands. PD-L1 high-expressing glioblastomas showed hypomethylation in 68% of all DMCGs. Interestingly, the list of the top 100 significantly differentially methylated genes showed the enrichment of regulatory RNAs with 19 DMCGs in miRNA, snoRNAs, lincRNAs, and asRNAs. Gene Ontology analysis showed the enrichment of post-transcriptional and RNA-associated pathways in the hypermethylated gene regions. In summary, dissecting the methylomes depending on PD-L1 status revealed significant alterations in RNA regulation and novel molecular targets in glioblastomas.

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EGFR Amplification Is a Phenomenon of IDH Wildtype and TERT Mutated High-Grade Glioma: An Integrated Analysis Using Fluorescence In Situ Hybridization and DNA Methylome Profiling

et al. 2022

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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.

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A patient with two gliomas with independent oligodendroglioma and glioblastoma biology proved by DNA-methylation profiling: a case report and review of the literature

Cited by 5 publications

References 11 publications

Anti-cancer and neuroprotective effects of conjugated graphene quantum dot in brain tumor-bearing rat model

Anti-cancer and neuroprotective effects of conjugated graphene quantum dot in brain tumor-bearing rat model

Methylome Profiling of PD-L1-Expressing Glioblastomas Shows Enrichment of Post-Transcriptional and RNA-Associated Gene Regulation

EGFR Amplification Is a Phenomenon of IDH Wildtype and TERT Mutated High-Grade Glioma: An Integrated Analysis Using Fluorescence In Situ Hybridization and DNA Methylome Profiling

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