Methylation data from radiation-induced glioma and reference cohort
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PROVIDER: PRJNA543820 | ENA |
REPOSITORIES: ENA
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Project description:Long-term complications such as radiation-induced second malignancies occur in a subset of patient following radiation-therapy, particularly relevant in pediatric patients due to the long follow-up period in case of survival. Radiation-induced gliomas (RIGs) have been reported in patients after treatment with cranial irradiation for various primary malignancies such as acute lymphoblastic leukemia (ALL) and medulloblastoma (MB). Our study revealed a unifying molecular signature for the majority of RIGs, with recurrent PDGFRA amplification and loss of CDKN2A/B and an absence of somatic hotspot mutations in genes encoding histone 3 variants or IDH1/2, uncovering diagnostic markers and potentially actionable targets.
2019-12-24 | GSE131482 | GEO
Project description:Radiation is the frontline treatment for malignant gliomas. Intra-tumoral heterogeneity has been proposed to grant cancer cells a superior trajectory and survival advantage to avoid therapeutic interventions including radiation. However, direct evidence to support the hypothesis via the transcriptome dynamics of glioma during radiation therapy is limited. The current study aim to measure the functional subpopulation dynamics before and after radiation treatment that assist the radiation resistance at single cell resolution. We investigate the single cell transcriptome and biological pathways of primary glioma mouse model and post-radiation early/late time point. Specifically, we used the RCAS mouse model for gliomas, which overexpress PDGFRA as the model. Using single cell transcriptome, for the first time, we confirmed the proneural classification of PDGFRA RCAS glioma mouse model and its heterogeneity. We found that recurrent dominant subpopulations are featured with elevated proliferation rate and hypoxia. In addition, we identified a subpopulation of radiation resistant cells in at early time points with elevated stemness. Lastly, the subpopulations composition undergoes large changes at late time point when the tumor recurred. Single cell transcriptome profiling of radiation treated mouse glioma mouse model identified tumor cell subpopulations dynamics. It provides novel insights into the molecular phenotype and biological functions of radiation resistant tumor cell population.
2016-12-01 | GSE76184 | GEO
Project description:This study addresses long-term effects of clinically relevant regimens of radiation in human glioma stem cells. Our investigations reveal a strikingly diverse spectrum of changes in cell behavior, gene expression patterns and tumor-propagating capacities evoked by radiation in different types of glioma stem cells. Evidence is provided that degree of cellular plasticity but not the propensity to self-renew is an important factor influencing radiation-induced changes in the tumor-propagating capacity of glioma stem cells. Gene expression analyses indicate that paralell transcriptomic responses to radiation underlie similarity of clinically relevant cellular outcomes such as the ability to promote tumor growth after radiation. Our findings underscore the importance of longitudinal characterizations of molecular and cellular responses evoked by cytotoxic treatrments in glioma stem cells.
2020-03-01 | GSE140746 | GEO
Project description:Data includes all available Affymetrix SNP data from a cohort of Pediatric malignant glioma samples, isolated from Formalin-fixed Paraffin embedded tissue. No clinical data is available. Copy number analysis of Affymetrix 250K Sty SNP arrays was performed for 28 pediatric malignant gliomas. The VN algorithm was used to generate the reference signal based on 48 Mapping 500k HapMap Trio Dataset template.
2011-11-23 | E-GEOD-25589 | biostudies-arrayexpress
Project description:Intra-tumor heterogeneity is a hallmark of glioblastoma multiforme, and thought to negatively affect treatment efficacy. Here we establish libraries of glioma-initiating cell (GIC) clones from patient samples and find extensive molecular and phenotypic variability between clones, including a wide range of responses to radiation and drugs. This widespread variability was observed as a continuum of multitherapy resistance phenotypes linked to a proneural-to-mesenchymal shift in the transcriptome.
2016-12-13 | GSE89400 | GEO
Project description:Background: One of the most serious complications of cranial radiotherapy is the development of radiation-induced glioma, which is estimated to occur in 1 to 4% of patients who have received cranial irradiation and has a worse prognosis than sporadic glioblastoma. To date, owing to its rarity, no standard of care has been established for radiation-induced glioma. Although comprehensive genetic analysis has recently uncovered the molecular characteristics of radiation-induced glioma, the full picture remains unclear, and the molecular features associated with treatment response and prognosis are poorly understood. Case presentation: A 45-year-old man presented with generalized seizures caused by multiple brain tumors involving the right frontal lobe, thalamus, and brainstem. The patient had a history of whole-brain radiotherapy for the recurrence of Burkitt's lymphoma at the age of 12. He underwent craniotomy, and the histological diagnosis was a high-grade glioma with isocitrate dehydrogenase-wildtype, which was presumed to be a radiation-induced glioma that developed 33 years after whole-brain irradiation. The Heidelberg DNA-methylation brain classifier most closely matched diffuse pediatric-type high-grade glioma, receptor tyrosine kinase-1 subtype, which is a typical methylation class of radiation-induced glioma. Methylation-specific polymerase chain reaction showed that the O6-methylguanine-DNA methyltransferase gene promoter was unmethylated. Next-generation sequencing identified CDKN2A/B deletion as well as co-amplification of several receptor tyrosine kinase-encoding genes including PDGFRA, KIT, and KDR, which are all located on chromosome 4q12. Amplification of this region is present broadly across cancers and is associated with a poor prognosis in sporadic glioblastoma. Nevertheless, the patient received conventional chemoradiotherapy with temozolomide. Subsequent multimodal imaging with magnetic resonance imaging and 11C-methionine positron emission tomography revealed complete remission of all lesions. Two years later, the patient is currently alive with a favorable performance status. Conclusions: Despite radiation-induced glioma with molecular features suggestive of an aggressive phenotype, our patient unexpectedly responded well to conventional chemoradiotherapy, resulting in complete remission that is exceptional in sporadic glioblastoma. Our case indicates that some of the radiation-induced gliomas may have distinct molecular characteristics involved in the therapeutic response that differ from those of sporadic glioblastomas.
2025-05-14 | GSE276059 | GEO
Project description:Glioblastoma is a malignant brain tumor that is highly resistant to radiation and chemotherapy, where patients survive on average only 15 months after diagnosis. Furthering the understanding of mechanisms leading to radiation resistance of glioma is paramount to identify novel therapeutic targets. Previous studies have shown that glioma stem cells (GSCs) play an important role in promoting radiation resistance and disease recurrence. Herein we analyze the proteomic alterations occurring in patient-derived GSCs upon radiation treatment in order to identify molecular drivers of resistance. We show that proteome changes upon radiation accurately predict the resistance status of the cells, and that resistance to radiation does not correlate with glioma transcriptional subtypes. We further show that the radio-resistant cell line GSC-267 sheds microvesicles (MVs) enriched in the metabolic enzyme nicotinamide phosphoribosyltransferase (NAMPT).
2023-04-06 | PXD030092 | Pride
Project description:Glioma initiating cells/stem cells exist in the bulk tumor of glioblastoma. This cell population contributes to the frequent resistances toward radiation/chemotherapy, aggressiveness of adult brain cancer and increased recurrence rate. Targeting stem cell population becomes one the most promising and permissive therapeutic strategies. We isolated glioma stem cells from patient-derived xenografts and profiled their epigenomic features, including 4 different DNA marks and 2 enhancer marks, and transcriptome in these in vitro cultured cell lines. Three fetal brain-derived neural stem/progenitors cells were used for comparing the unique and common molecular features in these glioma cancer stem cells.
2018-02-23 | GSE92462 | GEO
Project description:Comprehensive molecular characterization of pediatric radiation-induced high-grade glioma
| PRJNA732694 | ENA