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DNA methylation-based age acceleration observed in IDH wild-type glioblastoma is associated with better outcome - including in elderly patients

ABSTRACT: GBM samples (FFPE tissue) obtained from patients treated in clinical trials according to pre-specified clinical criteria (EORTC 26981/NCIC CE.3 pooled with the Lausanne Pilot trial, n=156).

ORGANISM(S): Homo sapiens

PROVIDER: GSE195640 | GEO | 2022/03/31

REPOSITORIES: GEO

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DNA methylation-based age acceleration observed in IDH wild-type glioblastoma is associated with better outcome - including in elderly patients [GBMnordic]

Project description:GBM samples (FFPE tissue) obtained from patients treated in clinical trials according to pre-specified clinical criteria (Nordic, n=116).

2022-03-31 | GSE195684 | GEO

DNA methylation-based age acceleration observed in IDH wild-type glioblastoma is associated with better outcome - including in elderly patients

Project description:DNA methylation-based age acceleration observed in IDH wild-type glioblastoma is associated with better outcome - including in elderly patients

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DNA methylation-based age acceleration observed in IDH wild-type glioblastoma is associated with better outcome - including in elderly patients [GBMnordic]

Project description:DNA methylation-based age acceleration observed in IDH wild-type glioblastoma is associated with better outcome - including in elderly patients [GBMnordic]

| PRJNA801707 | ENA

Homo sapiens

Project description:EORTC 10994 clinical trial

| PRJNA90875 | ENA

Evolving Treatment Strategies for Elderly Leukemia Patients with IDH Mutations.

Project description: Not available

| S-EPMC6025071 | biostudies-other

The methylome of DDR genes and benefit from RT or TMZ in IDH mutant low grade glioma treated in EORTC 22033

Project description:Treatment modalities for patients with low grade glioma (LGG) WHO grade II are controversial. Overall survival ranges from 2 to over 15 years depending on molecular and clinical factors. Hence, risk adjusted treatments are required to preserve cognitive function and quality of life. We aim at identifying mechanisms and associated molecular markers predicting benefit from radiotherapy (RT) or temozolomide (TMZ) on progression free survival in 120 isocitrate dehydrogenase 1 or 2 (IDHmt) mutant LGG treated in the randomized phase III trial EORTC 22033. IDH mutations, the characteristic hallmark of LGG, are associated with a CpG island methylator phenotype (CIMP). Given the genotoxic treatments in this study we determined the DNA methylome of DNA damage response (DDR) genes and assessed the association with progression free survival (PFS). We identified 62 functional CpGs corresponding to 24 of 410 DDR genes in the multidimensional LGG dataset from The Cancer Genome Atlas. Despite the low-powered study, the simulations suggested that seven CpGs, associated with 4 genes could be predictive for PFS in EORTC 22033. Most interestingly, two of the CpGs correspond to MGMT and consisted of the 2 probes used in the MGMT-STP27 classifier. The extent of methylation was predictive for PFS in the TMZ, but not the RT arm. LGG IDHmt and 1p and 19q codeleted that overlap largely with oligodendroglioma displayed a higher extent of MGMT methylation than the IDHmt non-codeleted tumors based on several independent LGG datasets. This is consistent with a better PFS of codeleted patients in the TMZ arm as compared to the non-codeleted patients, while no difference was observed in the RT-arm.

2018-01-31 | GSE104293 | GEO

Homo sapiens

Project description:p53 sequencing from the EORTC 10994 clinical trial

| PRJNA193388 | ENA

IDH-mutated astrocytomas with 19q-loss constitute a subgroup that confers better prognosis.

Project description: Not available

| S-EPMC6029820 | biostudies-other

Project description:The goal of the study was to identify a gene expression signature capable of predicting a pathological complete response following neoadjuvant anthracycline-based chemotherapy of breast cancer. The samples were taken from the FEC arm (5-fluorouracil, epirubicin, cyclophosphamide) of the EORTC 10994 trial. EORTC 10994 is a phase III clinical trial comparing FEC with ET (epirubicin, docetaxel) in patients with large operable, locally advanced or inflammatory breast cancer (www.eortc.be). Frozen biopsies were taken at randomisation. RNA was extracted from 100um thickness of 14G core needle biopsies. Adjacent sections were tested by H&E to confirm >20% tumour cell content. 200 ng total RNA per chip was amplified using the Affymetrix small sample protocol (IVT then Enzo). 102 tumours were tested on Affymetrix X3P chips. Single biopsies were tested per tumour. The CEL files were quantile normalised using rma. The clinical response measure was pathological complete response (pCR, disappearance of the tumour after chemotherapy with at most scattered invasive cells detected by histology). 102 tumors

2008-12-19 | E-GEOD-4779 | biostudies-arrayexpress

Pluripotent stem cell-derived corneal endothelial cells as an alternative to donor corneal endothelium in keratoplasty

Project description:Here, we evaluate the efficacy of cryopreserved human embryonic stem cell (hESC)-derived corneal endothelial cells (CECs) to form a functional monolayer of corneal endothelium (CE) in mammals (rabbits) and non-human primates (monkeys). We injected cryopreserved hESC-derived CECs in rabbits and monkeys either immediately after removing 8 mm of the central portion of the CE or a few days later when corneal edema developed. All clinical models developed deturgesced and clear corneas 2-3 weeks following the CEC injection and remained comparable to the CE of the untreated eye. Confocal scanning microscopy confirmed an intact structure of hexagonal/polygonal cells and immunohistochemical analysis illustrated a monolayer expressing barrier and pump function proteins in the regenerated CE. The necropsy examination confirmed no remarkable change in multiple tissues examined for teratoma formation. In conclusion, our data demonstrate the efficacy of cryopreserved hESC-derived CECs to form a functional CE on the denuded Descemet’s membrane.

2021-09-29 | GSE173692 | GEO

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