Global hypo-methylation in a proportion of glioblastoma enriched for an astrocytic signature is associated with increased invasion and altered immune landscape

Boot, James; Rosser, Gabriel; Kancheva, Dailya; Vinel, Claire; Lim, Yau Mun; Pomella, Nicola; Zhang, Xinyu; Guglielmi, Loredana; Sheer, Denise; Barnes, Michael R.; Brandner, Sebastian; Nelander, Sven; Movahedi, Kiavash; Marino, Silvia

doi:10.7554/elife.77335

Cited by 4 publications

(3 citation statements)

References 100 publications

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“…In the panel to the left the senescent astrocyte affects a neuron already exhibiting severe neurodegenerative defects. In the panel to the right the senescent astrocyte induces different effects on special forms of glioblastoma and astrocytoma: increasing invasiveness (top arrow) [62,63]; and impairing proliferation (bottom arrow) [64]. The present astrocyte and neuron images are analogous to those of [23].…”

Section: Role Of Senescent Astrocytes In Brain Diseasesmentioning

confidence: 74%

“…The top panel deals with a glioblastoma harboring a bias towards hypomethylation at defined methylated regions. Increased invasiveness of this cancer is induced by expression of astrocyte-type genes [62] (Figure 2, right, top arrow). Various forms of identified astrocytoma cancers, developing from mis-regulated genes expressed together with altered biological pathways, are being investigated [63].…”

Section: Role Of Senescent Astrocytes In Brain Cancersmentioning

confidence: 99%

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Role of Senescent Astrocytes in Health and Disease

Meldolesi

2023

IJMS

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For many decades after their discovery, astrocytes, the abundant glial cells of the brain, were believed to work as a glue, supporting the structure and metabolic functions of neurons. A revolution that started over 30 years ago revealed many additional functions of these cells, including neurogenesis, gliosecretion, glutamate homeostasis, assembly and function of synapses, neuronal metabolism with energy production, and others. These properties have been confirmed, limited however, to proliferating astrocytes. During their aging or following severe brain stress lesions, proliferating astrocytes are converted into their no-longer-proliferating, senescent forms, similar in their morphology but profoundly modified in their functions. The changed specificity of senescent astrocytes is largely due to their altered gene expression. The ensuing effects include downregulation of many properties typical of proliferating astrocytes, and upregulation of many others, concerned with neuroinflammation, release of pro-inflammatory cytokines, dysfunction of synapses, etc., specific to their senescence program. The ensuing decrease in neuronal support and protection by astrocytes induces the development, in vulnerable brain regions, of neuronal toxicity together with cognitive decline. Similar changes, ultimately reinforced by astrocyte aging, are also induced by traumatic events and molecules involved in dynamic processes. Senescent astrocytes play critical roles in the development of many severe brain diseases. The first demonstration, obtained for Alzheimer’s disease less than 10 years ago, contributed to the elimination of the previously predominant neuro-centric amyloid hypothesis. The initial astrocyte effects, operating a considerable time before the appearance of known Alzheimer’s symptoms evolve with the severity of the disease up to their proliferation during the final outcome. Involvement of astrocytes in other neurodegenerative diseases and cancer is now intensely investigated.

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Section: Role Of Senescent Astrocytes In Brain Diseasesmentioning

confidence: 74%

Section: Role Of Senescent Astrocytes In Brain Cancersmentioning

confidence: 99%

Role of Senescent Astrocytes in Health and Disease

Meldolesi

2023

IJMS

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“…Thus, DNA methylation is a reversible and dynamic process [72]; its impairment leads to a global or gene-specific hypomethylation or hypermethylation and the loss of imprinting, alterations that are frequently detected in cancer onset and progression [73][74][75][76][77][78].…”

Section: Dna Methylationmentioning

confidence: 99%

Epigenetics of Thymic Epithelial Tumors

Nicolì

Coppedè

2023

Cancers

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Thymic epithelial tumors (TETs) arise from the epithelial cells of the thymus and consist in the 1% of all adult malignancies, despite the fact that they are the most common lesions of the anterior mediastinum. TETs can be divided mainly into thymomas, thymic carcinomas, and the rarest ad aggressive neuroendocrine forms. Despite the surgical resection is quite resolving, the diagnosis of TETs is complicated by the absence of symptoms and the clinical presentation aggravated by several paraneoplastic disorders, including myasthenia gravis. Thus, the heterogeneity of TETs prompts the search for molecular biomarkers that could be helpful for tumor characterization and clinical outcomes prediction. With these aims, several researchers investigated the epigenetic profiles of TETs. In this manuscript, we narratively review the works investigating the deregulation of epigenetic mechanisms in TETs, highlighting the need for further studies combining genetic, epigenetic, and expression data to better characterize the different molecular subtypes and identify, for each of them, the most relevant epigenetic biomarkers of clinical utility.

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Unravelling the mosaic: Epigenetic diversity in glioblastoma

Lucchini,

Constantinou,

Marino

2024

Molecular Oncology

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Glioblastoma is the most common primary malignant brain tumour. Despite decades of intensive research in the disease, its prognosis remains poor, with an average survival of only 14 months after diagnosis. The remarkable level of intra‐ and interpatient heterogeneity is certainly contributing to the lack of progress in tackling this tumour. Epigenetic dysregulation plays an important role in glioblastoma biology and significantly contributes to intratumour heterogeneity. However, it is becoming increasingly clear that it also contributes to intertumour heterogeneity, which historically had mainly been linked to diverse genetic events occurring in different patients. In this review, we explore how DNA methylation, chromatin remodelling, microRNA (miRNA) dysregulation, and long noncoding RNA (lncRNA) alterations contribute to intertumour heterogeneity in glioblastoma, including its implications for advanced tumour stratification, which is the essential first step for developing more effective patient‐specific therapeutic approaches.

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Global hypo-methylation in a proportion of glioblastoma enriched for an astrocytic signature is associated with increased invasion and altered immune landscape

Cited by 4 publications

References 100 publications

Role of Senescent Astrocytes in Health and Disease

Role of Senescent Astrocytes in Health and Disease

Epigenetics of Thymic Epithelial Tumors

Unravelling the mosaic: Epigenetic diversity in glioblastoma

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