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

Abstract

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.

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

“…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.…”

“…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 ].…”

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

“…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 ].…”

Synthesis, Characterization, Molecular Docking and in vitro Anticancer Screening of Some Novel Thiophene Derivatives

“…A recent survey showed that around 3.2 cases per 1 lakh of population per year suffering from GBM and also showed a remarkably poor prognosis with only 26-33 % survival rate in 2 years and around 5 % survival in 5 years. [1][2][3][4][5][6][7][8][9][10][11][12] A significant progress has been made in making drugs for brain cancer or similar cancer through radiation therapy, resection techniques and chemotherapy but the survival of the median patient is significantly lower. [9,17] This short survival rate under modern medication forces us to further study the process of Glioblastoma Malignant with a better understanding.…”