scholarly journals Differential and Common Signatures of miRNA Expression and Methylation in Childhood Central Nervous System Malignancies: An Experimental and Computational Approach

Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5491
Author(s):  
George I. Lambrou ◽  
Myrto Poulou ◽  
Krinio Giannikou ◽  
Marios Themistocleous ◽  
Apostolos Zaravinos ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Central Nervous System ◽  
Nervous System ◽  
Mirna Expression ◽  
Tumor Staging ◽  
Gene Promoter ◽  
Tumor Type ◽  
Gene Methylation ◽  
Microarray Screening ◽  
And Control

Epigenetic modifications are considered of utmost significance for tumor ontogenesis and progression. Especially, it has been found that miRNA expression, as well as DNA methylation plays a significant role in central nervous system tumors during childhood. A total of 49 resected brain tumors from children were used for further analysis. DNA methylation was identified with methylation-specific MLPA and, in particular, for the tumor suppressor genes CASP8, RASSF1, MGMT, MSH6, GATA5, ATM1, TP53, and CADM1. miRNAs were identified with microarray screening, as well as selected samples, were tested for their mRNA expression levels. CASP8, RASSF1 were the most frequently methylated genes in all tumor samples. Simultaneous methylation of genes manifested significant results with respect to tumor staging, tumor type, and the differentiation of tumor and control samples. There was no significant dependence observed with the methylation of one gene promoter, rather with the simultaneous presence of all detected methylated genes’ promoters. miRNA expression was found to be correlated to gene methylation. Epigenetic regulation appears to be of major importance in tumor progression and pathophysiology, making it an imperative field of study.

scholarly journals A novel SMARCA2-CREM fusion: expanding the molecular spectrum of intracranial mesenchymal tumors beyond the FET genes

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Arnault Tauziède-Espariat ◽  
Gaëlle Pierron ◽  
Delphine Guillemot ◽  
Philipp Sievers ◽  
Dominique Cazals-Hatem ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Central Nervous System ◽  
Nervous System ◽  
Soft Tissue ◽  
Clear Cell ◽  
Clear Cell Sarcoma ◽  
World Health ◽  
Tumor Type ◽  
Cell Sarcoma ◽  
The Central Nervous System

AbstractA novel histomolecular tumor of the central nervous system, the “intracranial mesenchymal tumor (IMT), FET-CREB fusion-positive” has recently been identified in the literature and will be added to the 2021 World Health Organization Classification of Tumors of the Central Nervous System. However, our latest study using DNA-methylation analyses has revealed that intracranial FET-CREB fused tumors do not represent a single molecular tumor entity. Among them, the main subgroup presented classical features of angiomatoid fibrous histiocytoma, having ultrastructural features of arachnoidal cells, for. Another tumor type with clear cell component and histopathological signs of aggressivity clustered in close vicinity with clear cell sarcoma of soft tissue. Herein, we report one case of IMT with a novel SMARCA2-CREM fusion which has until now never been described in soft tissue or the central nervous system. We compare its clinical, histopathological, immunophenotypic, genetic and epigenetic features with those previously described in IMT, FET-CREB fusion-positive. Interestingly, the current case did not cluster with IMT, FET-CREB fusion-positive but rather presented histopathological (clear cell morphology with signs of malignancy), clinical (with a dismal course with several recurrences, metastases and finally the patient’s death), genetic (fusion implicating the CREM gene), and epigenetic (DNA-methylation profiling) similarities with our previously reported clear cell sarcoma-like tumor of the central nervous system. Our results added data suggesting that different clinical and histomolecular tumor subtypes or grades seem to be included within the terminology “IMT, FET-CREB fusion-positive”, and that further series of cases are needed to better characterize them.

scholarly journals QOL-36. USE OF CANNABINOIDS IN THE PEDIATRIC CENTRAL NERVOUS SYSTEM TUMOR POPULATION

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii438-iii438
Author(s):  
Kathleen Dorris ◽  
Jessica Channell ◽  
Ashley Mettetal ◽  
Molly Hemenway ◽  
Natalie Briones ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Central Nervous System ◽  
Nervous System ◽  
Cell Activity ◽  
Cns Tumors ◽  
Low Grade ◽  
Tumor Type ◽  
Central Nervous System Tumor ◽  
The Impact

Abstract BACKGROUND Cannabinoids, including cannabidiol (CBD) and tetrahydrocannabinol (THC), are a class of compounds found in marijuana. Numerous studies in adults have examined cannabinoid use in management of cancer-related symptoms such as nausea, anorexia, and pain. Less is known about the use in the pediatric oncology population. METHODS A prospective observational study has been ongoing since 2016 at Children’s Hospital Colorado to evaluate cannabinoids’ impact using PedsQL™ modules on quality of life of pediatric patients with central nervous system (CNS) tumors who are 2–18 years old. Laboratory assessments of T-cell activity and pharmacokinetics of CBD, THC and associated metabolites are in process. Diaries with exploratory information on cannabinoid use patterns are being collected. RESULTS Thirty-three patients (14:19; male:female) have been enrolled with a median age of 6.4 years (range, 2.9–17.7 years). The most common tumor type in enrolled patients is embryonal tumors (13/33; 39%). Nine (27%) patients have low-grade glial/glioneuronal tumors, and eight (24%) had high-grade/diffuse midline gliomas. The remaining patients had ependymoma or craniopharyngioma. The median time on cannabinoids is 9 months. Most (n=20) patients have used oral products with CBD and THC. One patient continues on cannabinoid therapy in follow up. Preliminary immune function analyses identified impaired neutrophil superoxide anion production and chemotaxis in patients taking cannabinoids at early time points on therapy. CONCLUSIONS Families of children with various CNS tumors are pursuing cannabinoid therapy for both antitumor and supportive care purposes. Analysis of the impact of cannabinoids on patients’ quality of life is ongoing.

scholarly journals High-grade astrocytoma with piloid features (HGAP): the Charité experience with a new central nervous system tumor entity

2021 ◽  
Author(s):  
Katja Bender ◽  
Eilís Perez ◽  
Mihaela Chirica ◽  
Julia Onken ◽  
Johannes Kahn ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Central Nervous System ◽  
Nervous System ◽  
World Health ◽  
Central Nervous System Tumor ◽  
High Grade ◽  
Thoracic Spinal Cord ◽  
High Grade Astrocytoma ◽  
Tumor Entity

Abstract Purpose High-grade astrocytoma with piloid features (HGAP) is a recently described brain tumor entity defined by a specific DNA methylation profile. HGAP has been proposed to be integrated in the upcoming World Health Organization classification of central nervous system tumors expected in 2021. In this series, we present the first single-center experience with this new entity. Methods During 2017 and 2020, six HGAP were identified. Clinical course, surgical procedure, histopathology, genome-wide DNA methylation analysis, imaging, and adjuvant therapy were collected. Results Tumors were localized in the brain stem (n = 1), cerebellar peduncle (n = 1), diencephalon (n = 1), mesencephalon (n = 1), cerebrum (n = 1) and the thoracic spinal cord (n = 2). The lesions typically presented as T1w hypo- to isointense and T2w hyperintense with inhomogeneous contrast enhancement on MRI. All patients underwent initial surgical intervention. Three patients received adjuvant radiochemotherapy, and one patient adjuvant radiotherapy alone. Four patients died of disease, with an overall survival of 1.8, 9.1, 14.8 and 18.1 months. One patient was alive at the time of last follow-up, 14.6 months after surgery, and one patient was lost to follow-up. Apart from one tumor, the lesions did not present with high grade histology, however patients showed poor clinical outcomes. Conclusions Here, we provide detailed clinical, neuroradiological, histological, and molecular pathological information which might aid in clinical decision making until larger case series are published. With the exception of one case, the tumors did not present with high-grade histology but patients still showed short intervals between diagnosis and tumor progression or death even after extensive multimodal therapy.

Special Considerations in Administering the Quick Test to Mentally Retarded and Central Nervous System-Impaired Subjects

1981 ◽  
Vol 49 (1) ◽  
pp. 308-310
Author(s):  
Bill D. Persinger
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Mentally Retarded ◽  
Self Perception ◽  
Quick Test ◽  
And Control

Eight special considerations are reported for use with the Quick Test (Ammons & Ammons, 1962) when testing mentally retarded or central nervous system-impaired subjects. Use of these techniques may result in a more accurate IQ. The techniques pertain to the manner of presenting stimuli, examiner's empathy, subject's self-perception, and control of guessing. The techniques are intended to supplement directions that appear in the Quick Test manual.

scholarly journals DNA methylation-based classification of central nervous system tumours

Nature ◽  
2018 ◽  
Vol 555 (7697) ◽  
pp. 469-474 ◽  
Author(s):  
David Capper ◽  
David T. W. Jones ◽  
Martin Sill ◽  
Volker Hovestadt ◽  
Daniel Schrimpf ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Central Nervous System ◽  
Nervous System ◽  
Central Nervous System Tumours

Tumors of the Central Nervous System

2013 ◽  
pp. 20-58
Author(s):  
Keith L. Ligon ◽  
Karima Mokhtari ◽  
Thomas W. Smith
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Molecular Biology ◽  
Tumor Type ◽  
Primary Tumors ◽  
System P ◽  
Precise Diagnosis ◽  
The Central Nervous System ◽  
Classification Of Tumors

This chapter presents the most up-to-date classification of tumors of the nervous system, based on the histological appearance of the neoplasm and also on information derived from cytogenetics and molecular biology, now recognized worldwide as increasingly important for more precise diagnosis, prognosis, and therapeutic guidance. The chapter provides a detailed morphologic description of each major tumor type, with numerous illustrations of macroscopic and microscopic lesions. First we consider primary tumors of the nervous system, including those derived from neuroepithelial tissue (astrocytic, oligodendroglial, ependymal, neuronal, and glioneuronal), pineal tissue, peripheral nerve sheath, and meninges. Next lymphomas, hematopoietic neoplasms, and secondary (metastatic) neoplasms are described.

scholarly journals DNA methylation temporal profiling following peripheral versus central nervous system axotomy

2014 ◽  
Vol 1 (1) ◽  
Author(s):  
Ricco Lindner ◽  
Radhika Puttagunta ◽  
Tuan Nguyen ◽  
Simone Di Giovanni
Keyword(s):  
Dna Methylation ◽  
Central Nervous System ◽  
Nervous System

scholarly journals Proteins in DNA methylation and their role in neural stem cell proliferation and differentiation

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Jiaqi Sun ◽  
Junzheng Yang ◽  
Xiaoli Miao ◽  
Horace H. Loh ◽  
Duanqing Pei ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Central Nervous System ◽  
Nervous System ◽  
Brain Plasticity ◽  
Dna Methyltransferases ◽  
Fine Tuning ◽  
Mammalian Brain ◽  
Main Body ◽  
Sequencing Technologies ◽  
Proliferation And Differentiation

Abstract Background Epigenetic modifications, namely non-coding RNAs, DNA methylation, and histone modifications such as methylation, phosphorylation, acetylation, ubiquitylation, and sumoylation play a significant role in brain development. DNA methyltransferases, methyl-CpG binding proteins, and ten-eleven translocation proteins facilitate the maintenance, interpretation, and removal of DNA methylation, respectively. Different forms of methylation, including 5-methylcytosine, 5-hydroxymethylcytosine, and other oxidized forms, have been detected by recently developed sequencing technologies. Emerging evidence suggests that the diversity of DNA methylation patterns in the brain plays a key role in fine-tuning and coordinating gene expression in the development, plasticity, and disorders of the mammalian central nervous system. Neural stem cells (NSCs), originating from the neuroepithelium, generate neurons and glial cells in the central nervous system and contribute to brain plasticity in the adult mammalian brain. Main body Here, we summarized recent research in proteins responsible for the establishment, maintenance, interpretation, and removal of DNA methylation and those involved in the regulation of the proliferation and differentiation of NSCs. In addition, we discussed the interactions of chemicals with epigenetic pathways to regulate NSCs as well as the connections between proteins involved in DNA methylation and human diseases. Conclusion Understanding the interplay between DNA methylation and NSCs in a broad biological context can facilitate the related studies and reduce potential misunderstanding.

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