Comparative proteogenomic characterization of glioblastoma

Asif, Samia; Fatima, Rawish; Krc, Rebecca; Bennett, Joseph; Raza, Shahzad

doi:10.2217/cns-2019-0003

Cited by 21 publications

(17 citation statements)

References 36 publications

(38 reference statements)

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“…The 4.1% (37/906) prevalence of F3T3 fusions identified in this study was compared to prevalence estimates reported in six previously published studies [ 2 , 5 , 17 , 33 , 34 , 39 ]. Taken together, the previously published studies involved a total of 883 IDH-wildtype GBMs (median, 68.5; range 17–584).…”

Section: Resultsmentioning

confidence: 88%

Genetic and epigenetic landscape of IDH-wildtype glioblastomas with FGFR3-TACC3 fusions

Mata

Benhamida

Lin

et al. 2020

acta neuropathol commun

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A subset of glioblastomas (GBMs) harbors potentially druggable oncogenic FGFR3-TACC3 (F3T3) fusions. However, their associated molecular and clinical features are poorly understood. Here we analyze the frequency of F3T3-fusion positivity, its associated genetic and methylation profiles, and its impact on survival in 906 IDH-wildtype GBM patients. We establish an F3T3 prevalence of 4.1% and delineate its associations with cancer signaling pathway alterations. F3T3-positive GBMs had lower tumor mutational and copy-number alteration burdens than F3T3-wildtype GBMs. Although F3T3 fusions were predominantly mutually exclusive with other oncogenic RTK pathway alterations, they did rarely co-occur with EGFR amplification. They were less likely to harbor TP53 alterations. By methylation profiling, they were more likely to be assigned the mesenchymal or RTK II subclass. Despite being older at diagnosis and having similar frequencies of MGMT promoter hypermethylation, patients with F3T3-positive GBMs lived about 8 months longer than those with F3T3-wildtype tumors. While consistent with IDH-wildtype GBM, F3T3-positive GBMs exhibit distinct biological features, underscoring the importance of pursuing molecular studies prior to clinical trial enrollment and targeted treatment.

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Section: Resultsmentioning

confidence: 88%

Genetic and epigenetic landscape of IDH-wildtype glioblastomas with FGFR3-TACC3 fusions

Mata

Benhamida

Lin

et al. 2020

acta neuropathol commun

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“…Recent evidence shows that FTO-mediated m 6 Am demethylation is an important regulatory mechanism in adjusting the stem-like properties of colorectal cancer cells [116], and many clues also imply that m 6 Am also emerges as an essential regulator in GBM (Figure 2, m 6 Am part). For instance, an integrated proteogenomic analysis in 17 GBM patient samples reveals that METTL4 is one of the top-ranked missense mutation genes [77]. DCP2 is upregulated in miR-338-5p overexpressed GBM cells and may participate in radiosensitivity and DNA damage response induced by miR-338-5p overexpression in GBM cells [78].…”

Section: Rna M 5 C Modification In Gbmmentioning

confidence: 99%

The Emerging Roles of RNA Modifications in Glioblastoma

Dong

Cui

2020

Cancers

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Glioblastoma (GBM) is a grade IV glioma that is the most malignant brain tumor type. Currently, there are no effective and sufficient therapeutic strategies for its treatment because its pathological mechanism is not fully characterized. With the fast development of the Next Generation Sequencing (NGS) technology, more than 170 kinds of covalent ribonucleic acid (RNA) modifications are found to be extensively present in almost all living organisms and all kinds of RNAs, including ribosomal RNAs (rRNAs), transfer RNAs (tRNAs) and messenger RNAs (mRNAs). RNA modifications are also emerging as important modulators in the regulation of biological processes and pathological progression, and study of the epi-transcriptome has been a new area for researchers to explore their connections with the initiation and progression of cancers. Recently, RNA modifications, especially m6A, and their RNA-modifying proteins (RMPs) such as methyltransferase like 3 (METTL3) and α-ketoglutarate-dependent dioxygenase alkB homolog 5 (ALKBH5), have also emerged as important epigenetic mechanisms for the aggressiveness and malignancy of GBM, especially the pluripotency of glioma stem-like cells (GSCs). Although the current study is just the tip of an iceberg, these new evidences will provide new insights for possible GBM treatments. In this review, we summarize the recent studies about RNA modifications, such as N6-methyladenosine (m6A), N6,2′O-dimethyladenosine (m6Am), 5-methylcytosine (m5C), N1-methyladenosine (m1A), inosine (I) and pseudouridine (ψ) as well as the corresponding RMPs including the writers, erasers and readers that participate in the tumorigenesis and development of GBM, so as to provide some clues for GBM treatment.

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“…GBM patients present with only a 15-to 19-month median overall survival rate due to chemoradiotherapy resistance and recurrence (1). Recent studies have identified several molecular alterations involved in GBM carcinogenesis, progression, chemotherapeutic resistance and recurrence, such as IDH1, 1p/19q, MGMT, ATRX and PTEN, but the precise mechanisms underlying this malignancy and its rapid recurrence have not been fully elucidated (2)(3)(4). Targeting key genes and signaling pathways is considered a promising approach for the diagnosis and treatment of cancer.…”

Section: Introductionmentioning

confidence: 99%

ZWINT: A potential therapeutic biomarker in patients with glioblastoma correlates with cell proliferation and invasion

et al. 2020

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Glioblastoma (GBM) is the most aggressive primary intracranial tumor in adults. Chemoradiotherapy resistance and recurrence after surgery are the main malignant progression factors, leading to a high mortality rate. Therefore, the exploration of novel biomarkers and molecular mechanisms of GBM is urgent. Differentially expressed genes (DEGs) of GBM were screened in a TCGA dataset. Homo sapiens ZW10 interacting kinetochore protein (ZWINT) was found to be upregulated in GBM, which was confirmed by immunohistochemical staining of a tissue microarray. Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID) database. A protein-protein interaction (PPI) network was established by the STRING database, and hub genes were visualized by Cytoscape. The correlation results were verified with the GSE15824 dataset. Bioinformatic analysis confirmed that ZWINT was significantly positively correlated with kinetochore protein NDC80 homolog (NDC80), serine/threonine-protein kinase PLK1 (PLK1) and spindle and kinetochore associated complex subunit 1 (SKA1) and together are involved in regulating mitosis and the cell cycle of GBM. ZWINT expression was knocked down in U251 and U87 MG GBM cells by lentiviral vectors carrying a small hairpin RNA (shRNA) targeting ZWINT. The effect of ZWINT silencing on cell proliferation, invasion and apoptosis was determined by the Celigo assay, MTT assay, Transwell assay, flow cytometry and caspase-3/7 assay in vitro. A subcutaneous xenograft tumor model was established to explore the influence of ZWINT knockdown on GBM growth in vivo. Our preliminary study demonstrated that ZWINT knockdown effectively inhibited proliferation and invasion and induced apoptosis of GBM cells and notably suppressed GBM growth in vivo. Therefore, we speculate that ZWINT may be a potential therapeutic biomarker for GBM, with NDC80 and PLK1 conjointly involved in regulating cell division and the mitotic cell cycle.

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Comparative proteogenomic characterization of glioblastoma

Cited by 21 publications

References 36 publications

Genetic and epigenetic landscape of IDH-wildtype glioblastomas with FGFR3-TACC3 fusions

Genetic and epigenetic landscape of IDH-wildtype glioblastomas with FGFR3-TACC3 fusions

The Emerging Roles of RNA Modifications in Glioblastoma

ZWINT: A potential therapeutic biomarker in patients with glioblastoma correlates with cell proliferation and invasion

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