IDH1- and IDH2-mutations in brain glial tumors - the new antioncogenic mechanism

Demyashkin, Grigory; Никитин, П.В.

doi:10.17116/jnevro201811841134-139

Cited by 7 publications

(4 citation statements)

References 40 publications

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“…Recent research has focused on the aberrant molecular alterations in gliomas. IDH1/2 mutation (Demyashkin and Nikitin, 2018), 1p/19q codeletion (Cairncross et al, 1998), TERT promoter mutation (Arita et al, 2016) and several other markers are used to define glioma subtypes (Eckel-Passow et al, 2015). Despite improvements in therapeutic strategies, there has been no substantial improvement in glioma patient OS, especially for GBM patients, over the past decade, partially because of poorly understood mechanisms of GBM initiation and progression.…”

Section: Introductionmentioning

confidence: 99%

Identifying Differential Expression Genes and Prognostic Signature Based on Subventricular Zone Involved Glioblastoma

et al. 2022

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Background: Studies have suggested that glioblastoma (GBM) cells originate from the subventricular zone (SVZ) and that GBM contact with the SVZ correlated with worse prognosis and higher recurrence. However, research on differentially expressed genes (DEGs) between GBM and the SVZ is lacking.Methods: We performed deep RNA sequencing on seven SVZ-involved GBMs and paired tumor-free SVZ tissues. DEGs and enrichment were assessed. We obtained GBM patient expression profiles and clinical data from the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) databases. The least absolute shrinkage and selection operator Cox regression model was utilized to construct a multigene signature in the CGGA cohort. GBM patient data from TCGA cohort were used for validation.Results: We identified 137 (97 up- and 40 down-regulated) DEGs between GBM and healthy SVZ samples. Enrichment analysis revealed that DEGs were mainly enriched in immune-related terms, including humoral immune response regulation, T cell differentiation, and response to tumor necrosis factor, and the MAPK, cAMP, PPAR, PI3K-Akt, and NF-κb signaling pathways. An eight-gene (BCAT1, HPX, NNMT, TBX5, RAB42, TNFRSF19, C16orf86, and TRPC5) signature was constructed. GBM patients were stratified into two risk groups. High-risk patients showed significantly reduced overall survival compared with low-risk patients. Univariate and multivariate regression analyses indicated that the risk score level represented an independent prognostic factor. High risk score of GBM patients negatively correlated with 1p19q codeletion and IDH1 mutation. Immune infiltration analysis further showed that the high risk score was negatively correlated with activated NK cell and monocyte counts, but positively correlated with macrophage and activated dendritic cell counts and higher PD-L1 mRNA expression.Conclusion: Here, a novel gene signature based on DEGs between GBM and healthy SVZ was developed for determining GBM patient prognosis. Targeting these genes may be a therapeutic strategy for GBM.

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Section: Introductionmentioning

confidence: 99%

Identifying Differential Expression Genes and Prognostic Signature Based on Subventricular Zone Involved Glioblastoma

et al. 2022

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“…При этом мутации генов IDH1 и IDH2 предполагаются в качестве ранних молекулярных событий в ходе канцерогенеза глиом. В связи с этим ряд исследователей предполагает, что данные мутации являются ключевыми ранними молекулярными изменениями, способствующими возникновению и прогрессированию диффузных глиальных опухолей [10].…”

Section: роль мутаций в генах Idh1 и Idh2 и современная классификацияunclassified

Glioblastoma molecular and histological heterogeneity

Никитин

Ryzhova

Потапов

et al. 2020

Clin. Exp. Morphology

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The heterogeneity of tumors properties is a serious diagnostic and therapeutic problem. It is manifested by the variability of genetic, proteomic and epigenetic parameters both between different samples of the same histological variant of the tumor, and between different sites within the same neoplasm with the presence of heterogeneous cell populations in this particular patient. Glioblastoma (GB) is one of the most frequent fatal tumors of the central nervous system in humans. The understanding the intertumor heterogeneity is the key to the development of both new diagnostic approaches and innovative personalized methods of patients’ management. In the framework of this review, the main data on intertumor heterogeneity of GB are sum-marized. The basic genetic, epigenetic and proteomic aspects of the modern understanding of GB molecular profile and intertumor heterogeneity are considered. Keywords: glioblastoma, intertumor heterogeneity, glioblastoma genetics, mutations

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“…In recent years, research has focused on aberrant molecular alterations in gliomas. IDH1/2 mutation, 5 1p/19q co‐deletion, 6 TERT promoter mutation 7 and several other markers have been used to define subtypes of gliomas. However, there are few therapeutic targets with potential clinical applications.…”

Section: Introductionmentioning

confidence: 99%

Highly expressed of SERPINA3 indicated poor prognosis and involved in immune suppression in glioma

Yuan

Wang

Zhang

et al. 2021

Immunity Inflam & Disease

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Introduction The prognosis of patients with glioma is dismal. It has been reported that Serpin peptidase inhibitor clade A member 3 (SERPINA3) is associated with the mobility and invasion of tumor cells. Our study was designed to explore the value of SERPINA3 messenger RNA (mRNA) expression in the biological process, prognosis, and immune significance in glioma. Methods We analyzed the biological functions of SERPINA3 through data from the Chinese Glioma Genome Atlas databases. Differentially expressed genes and enrichment analysis were performed and correlations between SERPINA3 expression and immune cell infiltration were analyzed. Further, we validated the expression and the survival prediction role of SERPINA3 by using tissue microarrays and RNAscope in situ hybridization in 321 gliomas. The correlations between the expression and clinical‐pathological parameters as well as other biomarkers were examined. Results Univariate and multivariate regression both indicated that the level of SERPINA3 transcript represented an independent prognostic factor. High levels of SERPINA3 correlated with poor survival in patients with glioma. Expression of SERPINA3 mRNA was observed positively correlated with MCM6, IGFBP2, and FKBP10. Enrichment analysis showed SERPINA3 mainly enriched in immune‐related terms and signaling pathways including MAPK, TNF, P53, PI3K‐Akt, nuclear factor‐κB. Immune infiltration analysis further declare the SERPINA3 expression negatively correlated with levels of Macrophages M1, native CD4+ T cell, monocytes, and Mast cell activated. And overexpression of SERPINA3 correlated with low CD4+ T cell infiltration in glioma tissues. Conclusions SERPINA3 may play a key role in the biological process of glioma cells especially in immune suppression activities. SERPINA3 may serve as an independent survival prediction factor in glioma patients.

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IDH1- and IDH2-mutations in brain glial tumors - the new antioncogenic mechanism

Cited by 7 publications

References 40 publications

Identifying Differential Expression Genes and Prognostic Signature Based on Subventricular Zone Involved Glioblastoma

Identifying Differential Expression Genes and Prognostic Signature Based on Subventricular Zone Involved Glioblastoma

Glioblastoma molecular and histological heterogeneity

Highly expressed of SERPINA3 indicated poor prognosis and involved in immune suppression in glioma

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