The utility of DNA methylation analysis in elderly patients with pilocytic astrocytoma morphology

Suruga, Yasuki; Satomi, Kaishi; Otani, Yoshihiro; Fujii, Kentaro; Ishida, Joji; Uneda, Atsuhito; Tsuboi, Nobushige; Makino, Keigo; Hirano, Shuichiro; Kemmotsu, Naoya; Imoto, Ryoji; Mizuta, Ryo; Tomita, Yusuke; Yasuhara, Takao; Washio, Kana; Yanai, Hiroyuki; Matsushita, Yuko; Hibiya, Yuko; Yoshida, Akihiko; Capper, David; Ichimura, Koichi; Date, Isao

doi:10.1007/s11060-022-04131-3

Cited by 4 publications

(4 citation statements)

References 23 publications

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“…However, HGAP frequently presents with alterations in mitogen‐activated protein kinase (MAPK) pathway genes, often co‐occurring with a homozygous deletion involving the CDKN2A and/or CDKN2B locus, ATRX mutation, or loss of nuclear ATRX expression 52,54,55 . Because of various morphological findings, HGAP cannot be excluded, particularly in elderly patients with PA‐like morphology 56 . A recent study has identified an epigenetically and clinically distinct subtype associated with neurofibromatosis type 1 in patients with HGAP 57 …”

Section: Genome‐wide Dna Methylome‐based Classification Of Cns Tumorsmentioning

confidence: 99%

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Decoding the DNA methylome of central nervous system tumors: An emerging modality for integrated diagnosis

Satomi,

Ichimura,

Shibahara

2024

Pathology International

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The definitive diagnosis and classification of individual cancers are crucial for patient care and cancer research. To achieve a robust diagnosis of central nervous system (CNS) tumors, a genotype‐phenotype integrated diagnostic approach was introduced in recent versions of the World Health Organization classification, followed by the incorporation of a genome‐wide DNA methylome‐based classification. Microarray‐based platforms are widely used to obtain DNA methylome data, and the German Cancer Research Center (Deutsches Krebsforschungszentrum [DKFZ]) has a webtool for a DNA methylation‐based classifier (DKFZ classifier). Integration of DNA methylome will further enhance the precision of CNS tumor classification, especially in diagnostically challenging cases. However, in the clinical application of DNA methylome‐based classification, challenges related to data interpretation persist, in addition to technical caveats, regulations, and limited accessibility. Dimensionality reduction (DMR) can complement integrated diagnosis by visualizing a profile and comparing it with other known samples. Therefore, DNA methylome‐based classification is a highly useful research tool for auxiliary analysis in challenging diagnostic and rare disease cases, and for establishing novel tumor concepts. Decoding the DNA methylome, especially by DMR in addition to DKFZ classifier, emphasizes the capability of grasping the fundamental biological principles that provide new perspectives on CNS tumors.

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Section: Genome‐wide Dna Methylome‐based Classification Of Cns Tumorsmentioning

confidence: 99%

“…52,54,55 Because of various morphological findings, HGAP cannot be excluded, particularly in elderly patients with PA-like morphology. 56 A recent study has identified an epigenetically and clinically distinct subtype associated with neurofibromatosis type 1 in patients with HGAP. 57…”

Section: Hgapmentioning

confidence: 99%

Decoding the DNA methylome of central nervous system tumors: An emerging modality for integrated diagnosis

Satomi,

Ichimura,

Shibahara

2024

Pathology International

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“…For quite some time this cancer had been attributed with a good prognosis. With older patients, however, adequate DNA analyses have revealed negative prognoses [98]. Two additional approaches to glioblastoma have investigated the astrocytic potential against cancer.…”

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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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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“…Integrating traditional histological and molecular techniques is also expected to enhance prognostic assessments of brain tumors [15]. It is considered appropriate to classify a tumor as malignant if characteristic molecular alterations are present, even if histological examination suggests a lower grade of malignancy [8,16].…”

Section: Introductionmentioning

confidence: 99%

Variances in the Expression Profile of Circadian Clock-Related Genes in Astrocytic Brain Tumors

Staszkiewicz,

Sobański,

Pulka

et al. 2024

Cancers

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This study explores the role of circadian clock genes in the progression of astrocytic tumors, a prevalent type of brain tumor. The aim was to assess the expression patterns of these genes in relation to the tumor grade. Using microarray analysis, qRT-PCR, and methylation-specific PCR, we examined gene expression, DNA methylation patterns, and microRNA interactions in tumor samples from 60 patients. Our results indicate that the expression of key circadian clock genes, such as clock circadian regulator (CLOCK), protein kinase AMP-activated catalytic subunit alpha 1 (PRKAA1), protein kinase AMP-activated catalytic subunit alpha 2 (PRKAA2), protein kinase AMP-activated non-catalytic subunit beta 1 (PRKAB1), protein kinase AMP-activated non-catalytic subunit beta 2 (PRKAB2), period circadian regulator 1 (PER1), period circadian regulator 2 (PER2) and period circadian regulator 3 (PER3), varies significantly with the tumor grade. Notably, increased CLOCK gene expression and protein levels were observed in higher-grade tumors. DNA methylation analysis revealed that the promoter regions of PER1-3 genes were consistently methylated, suggesting a mechanism for their reduced expression. Our findings also underscore the complex regulatory mechanisms involving miRNAs, such as hsa-miR-106-5p, hsa-miR-20b-5p, and hsa-miR-30d-3p, which impact the expression of circadian clock-related genes. This underscores the importance of circadian clock genes in astrocytic tumor progression and highlights their potential as biomarkers and therapeutic targets. Further research is needed to validate these results and explore their clinical implications.

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The utility of DNA methylation analysis in elderly patients with pilocytic astrocytoma morphology

Cited by 4 publications

References 23 publications

Decoding the DNA methylome of central nervous system tumors: An emerging modality for integrated diagnosis

Decoding the DNA methylome of central nervous system tumors: An emerging modality for integrated diagnosis

Role of Senescent Astrocytes in Health and Disease

Variances in the Expression Profile of Circadian Clock-Related Genes in Astrocytic Brain Tumors

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