Loss of p53 Concurrent with RAS and TERT Activation Induces Glioma Formation

Gong, Meiting; Fan, Xiaoqing; Yu, Huihan; Niu, Wanxiang; Sun, Suling; Wang, Hongzhi; Chen, Xueran

doi:10.1007/s12035-023-03288-w

Cited by 8 publications

(6 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the contrary, some found that RNAi inhibition of p53 function or homozygously knocked-out TP53 failed to induce TERT expression in osteosarcoma and colon cancer cells. 24,25 The different results might be associated with tumor cell-type specificity and interaction with complicated factors affecting p53 function. Though TP53 presented without mutation, this case showed overexpression for p53 in the fibrosarcomatous area but a wild-type pattern in the storiform area, indicating a potential correlation of overexpressed p53 with tumor progression.…”

Section: Discussionmentioning

confidence: 99%

“…Several investigations found that the p53 function defects (such as TP53 mutation) led to the TERT upregulation and telomerase activity in experimental human neural stem cells and mammary epithelial cells. On the contrary, some found that RNAi inhibition of p53 function or homozygously knocked‐out TP53 failed to induce TERT expression in osteosarcoma and colon cancer cells 24,25 . The different results might be associated with tumor cell‐type specificity and interaction with complicated factors affecting p53 function.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

COL1A1::PDGFB fusion uterine sarcoma with a TERT promoter mutation

Lu,

Chen,

Zeng

et al. 2023

Genes Chromosomes & Cancer

View full text Add to dashboard Cite

COL1A1::PDGFB fusion uterine sarcoma is a rare uterine mesenchymal tumor with some clinicopathological features that overlap with those of soft tissue dermatofibrosarcoma protuberans. However, the varied clinicopathologic and genetic characteristics have not been fully revealed, which may be a potential pitfall for diagnosis. Here, we present a case of COL1A1::PDGFB fusion‐positive uterine sarcoma in a 49‐years‐old female. Histologically, the tumor from the initial marginal excision predominantly exhibited high‐grade fibrosarcomatous and myxofibrosarcoma‐like appearances, while a low‐grade focal area displaying storiform growth was identified in the residual tumor after subsequently extended resection. Immunohistochemically, the high‐grade components mainly exhibited focal positivity for CD34 and mutated‐type p53 immunoreactivity, whereas the low‐grade component showed diffuse positivity for CD34 and wild‐type p53 staining. The COL1A1::PDGFB fusion was confirmed by fluorescence in situ hybridization and next‐generation sequencing. In addition, the TERT‐124 C > T mutation was further identified in this lesion's fibrosarcomatous and classic storiform components. To the best of our knowledge, this is the first described case of COL1A1::PDGFB fusion uterine sarcoma with a TERT promoter mutation, which might be a novel genetic finding associated with tumorigenesis of this rare tumor.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

COL1A1::PDGFB fusion uterine sarcoma with a TERT promoter mutation

Lu,

Chen,

Zeng

et al. 2023

Genes Chromosomes & Cancer

View full text Add to dashboard Cite

show abstract

“…In addition to its role in regulating H3K27 trimethylation [39], EZH2 is also capable of regulating its downstream targets in a PRC2-and methylation-independent manner. In the context of glioma, recent research has highlighted EZH2 as an oncogene [40,41]. Studies have demonstrated that inhibition of EZH2 expression can impair glioma cell self-renewal in vitro and tumor initiation capacity in vivo, while also enhancing drug and radiotherapy sensitivity and improving patient survival [40][41][42].…”

Section: The Relationship Between Ezh 2 Expression Levels In Glioma T...mentioning

confidence: 99%

“…In the context of glioma, recent research has highlighted EZH2 as an oncogene [40,41]. Studies have demonstrated that inhibition of EZH2 expression can impair glioma cell self-renewal in vitro and tumor initiation capacity in vivo, while also enhancing drug and radiotherapy sensitivity and improving patient survival [40][41][42]. However, prior to this investigation, the relationship between EZH2 expression levels and glioma pathological grade, IDH1/2 mutation status, 1p/19q status, and prognosis had not been extensively characterized.…”

Section: The Relationship Between Ezh 2 Expression Levels In Glioma T...mentioning

confidence: 99%

Overexpression of EZH2 is associated with clinicopathological parameters and poor prognosis in gliomas

Peng,

Chen,

Yang

et al. 2024

Preprint

View full text Add to dashboard Cite

Histone methyltransferase EZH2, primarily localized in the nucleus, mediates constitutive Polycomb repressive complex activity by trimethylating lysine 27 of histone H3 (H3K27me3), leading to gene silencing through canonical and noncanonical mechanisms, resulting in transcriptional repression or activation. Its involvement is crucial in cell growth, proliferation, differentiation, and apoptosis, with its effects linked to the regulation of various targets and signaling pathways. Overexpression of EZH2 alters gene expression and function, thereby facilitating cancer progression. Recent research has identified the potential prognostic role of EZH2 expression in glioma patients. This study assesses the clinicopathological significance and prognostic value of EZH2 expression in gliomas using available data. The mRNA levels of EZH2 in tumor tissues and normal tissues were assessed using timer2.0 and data from CGCA and TGCA. The prognostic significance of EZH2 mRNA expression was determined using Kaplan-Meier plotter. A total of 147 clinical samples from glioma patients underwent immunohistochemistry analysis to evaluate EZH2 protein expression. Cox proportional hazards regression model and Kaplan-Meier survival curves were employed to assess the relationship between EZH2 expression, clinicopathological parameters, and overall survival (OS). Across multiple tumor cohorts, EZH2 was found to be upregulated and amplified in tumor tissues. In high-grade glioma patients, EZH2 expression was significantly increased, and higher EZH2 expression correlated with poorer OS, disease-specific survival (DSS), and progression-free interval (PFI). Therefore, the level of EZH2 may serve as a prognostic biomarker for glioma patients.

show abstract

“…In vivo and in vitro experiments have shown that in gliomas with mutations in human TP53 (tumor protein P53), zDHHC5 mediates enhancer of EZH2 (zeste homolog 2) palmitoylation, leading to an altered phosphorylation state of EZH2 that drives glioma development ( Gong et al, 2023 ). Overexpression or knockdown of zDHHC5 affected cell growth, the cell cycle, self-renewal and invasiveness, and the expression level of zDHHC5 was inversely associated with the overall survival of glioma patients ( Chen et al, 2017 ).…”

Section: The Role Of Zdhhc In Neurological Diseasesmentioning

confidence: 99%

The role of s-palmitoylation in neurological diseases: implication for zDHHC family

Liao,

Huang,

Liu

et al. 2024

Front. Pharmacol.

View full text Add to dashboard Cite

S-palmitoylation is a reversible posttranslational modification, and the palmitoylation reaction in human-derived cells is mediated by the zDHHC family, which is composed of S-acyltransferase enzymes that possess the DHHC (Asp-His-His-Cys) structural domain. zDHHC proteins form an autoacylation intermediate, which then attaches the fatty acid to cysteine a residue in the target protein. zDHHC proteins sublocalize in different neuronal structures and exert dif-ferential effects on neurons. In humans, many zDHHC proteins are closely related to human neu-rological disor-ders. This review focuses on a variety of neurological disorders, such as AD (Alz-heimer’s disease), HD (Huntington’s disease), SCZ (schizophrenia), XLID (X-linked intellectual disability), attention deficit hyperactivity disorder and glioma. In this paper, we will discuss and summarize the research progress regarding the role of zDHHC proteins in these neu-rological disorders.

show abstract

Loss of p53 Concurrent with RAS and TERT Activation Induces Glioma Formation

Cited by 8 publications

References 43 publications

COL1A1::PDGFB fusion uterine sarcoma with a TERT promoter mutation

COL1A1::PDGFB fusion uterine sarcoma with a TERT promoter mutation

Overexpression of EZH2 is associated with clinicopathological parameters and poor prognosis in gliomas

The role of s-palmitoylation in neurological diseases: implication for zDHHC family

Contact Info

Product

Resources

About