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DNA methylome evolution and reprogramming in recurrent glioblastoma

ABSTRACT: DNA methylome evolution and reprogramming in recurrent glioblastoma

PROVIDER: PRJNA437625 | ENA |

REPOSITORIES: ENA

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DNA methylome evolution and reprogramming in recurrent glioblastoma

Project description:Recurrent glioblastoma (GBM) has a grim prognosis, though MGMT promoter methylation and IDH mutation provide a significant survival advantage. The product of IDH mutation, 2-hydroxyglutarate, increases global DNA methylation by inhibiting demethylases. While lower-grade IDH-mutant gliomas demonstrate increased methylation as a result of this process, DNA becomes relatively hypomethylated during progression from low-grade glioma to secondary (IDH-mutant) GBM. Here we show that global DNA hypomethylation also occurs during primary (IDH-wild type) GBM recurrence. Moreover, in a phase I trial of 14 patients with recurrent (IDH-wild type) GBM, we targeted DNA hypomethylation using a methyl donor treatment. In autopsied tumors from patients treated, we observed a global increase in DNA methylation compared to initial tumor. These results suggest that hypomethylation is a marker for recurrence, and its reprogramming represents a potential therapeutic vulnerability.

2021-12-31 | GSE111627 | GEO

Genomic-Enabled Medicine for Recurrent Glioblastoma

Project description:Genomic-Enabled Medicine for Recurrent Glioblastoma

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Genomic-Enabled Medicine for Recurrent Glioblastoma

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The FFPE samples of the primary vs. recurrent glioblastoma validation cohort

Project description:The FFPE samples of the primary vs. recurrent glioblastoma validation cohort

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Reversal of Aberrant Cancer Methylome and Transcriptome upon Direct Reprogramming of Lung Cancer Cells.

Project description:This SuperSeries is composed of the following subset Series: GSE35911: Reversal of Aberrant Cancer Methylome and Transcriptome upon Direct Reprogramming of Lung Cancer Cells [Expression] GSE35912: Reversal of Aberrant Cancer Methylome and Transcriptome upon Direct Reprogramming of Lung Cancer Cells [Methylation] Refer to individual Series

2012-08-27 | E-GEOD-35913 | biostudies-arrayexpress

EGFR pathway expression persists in recurrent glioblastoma independent of amplification status

Project description:Background: Glioblastoma mortality is driven by tumour progression or recurrence despite administering a therapeutic arsenal consisting of surgical resection, radiation, and alkylating chemotherapy. The genetic changes underlying tumour progression and chemotherapy resistance are poorly understood. Methods: In this work, we sought to define the relationship between EGFR amplification status, EGFR mRNA expression, and EGFR pathway activity. We compared RNA-sequencing data from matched primary and recurrent tumour samples (N = 40 patients, 20 with EGFR amplification). Results: In the setting of glioblastoma recurrence, the EGFR pathway was overexpressed regardless of EGFR amplification status, suggesting a common genomic endpoint in recurrent glioblastoma, although EGFR amplification did associate with higher EGFR mRNA expression. Three of forty patients in the study cohort had EGFR-amplified tumours and received targeted EGFR therapy. Their molecular subtypes and clinical outcomes did not significantly differ from patients who received conventional chemotherapy. Conclusion: Our findings suggest that while the EGFR amplification may confer a unique molecular profile in primary glioblastoma, pathway analysis reveals upregulation of the EGFR pathway in recurrence, regardless of amplification status. As such, the EGFR pathway may be a key mediator of glioblastoma progression.

2023-01-25 | GSE222515 | GEO

Expression pattern of circRNA in primary and recurrent glioblastoma.

Project description:Expression pattern of circRNA in primary and recurrent glioblastoma.

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Gene expression profiles of non-recurrent human glioblastoma tumorspheres

Project description:Gene expression profiles of non-recurrent human glioblastoma tumorspheres

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Gene expression profiles of non-recurrent human glioblastoma tissues

Project description:Gene expression profiles of non-recurrent human glioblastoma tissues

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Transcriptional changes induced by bevacizumab combination therapy in responding and non-responding recurrent glioblastoma patients

Project description:Purpose: To identify transcriptional changes by RNA-seq in tumor samples, before bevacizumab combination treatment and after bevacizumab combination treatment in both responding and non-responding recurrent glioblastoma patients

2017-04-20 | GSE79671 | GEO

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