scholarly journals PDTM-43. THE ROLE OF TUMOR ASSOCIATED MACROPHAGES IN PEDIATRIC HIGH-GRADE GLIOMA

2018 ◽  
Vol 20 (suppl_6) ◽  
pp. vi213-vi213
Author(s):  
James Ross ◽  
Zhihong Chen ◽  
Frank Szulzewsky ◽  
Matthew Schniederjan ◽  
Oren Becher ◽  
...  
Keyword(s):  
High Grade Glioma ◽  
High Grade ◽  
Tumor Associated Macrophages ◽  
Pediatric High Grade Glioma

Investigating the role of poly-(ADP-Ribose)-polymerase as a therapeutic target in pediatric high grade glioma

2013 ◽  
Vol 333 ◽  
pp. e603
Author(s):  
Y. Chornenkyy ◽  
S. Agnihotri ◽  
P. Buczkowicz ◽  
P. Rakopoulos ◽  
O. Becher ◽  
...  
Keyword(s):  
Therapeutic Target ◽  
High Grade Glioma ◽  
High Grade ◽  
Pediatric High Grade Glioma

scholarly journals Hemispherical Pediatric High-Grade Glioma: Molecular Basis and Therapeutic Opportunities

2020 ◽  
Vol 21 (24) ◽  
pp. 9654
Author(s):  
Santiago Haase ◽  
Fernando M. Nuñez ◽  
Jessica C. Gauss ◽  
Sarah Thompson ◽  
Emily Brumley ◽  
...  
Keyword(s):  
Cell Biology ◽  
High Grade Glioma ◽  
Cerebral Hemispheres ◽  
Clinical State ◽  
Molecular Characteristics ◽  
High Grade ◽  
Molecular Alterations ◽  
Current Therapies ◽  
Pediatric High Grade Glioma

In this review, we discuss the molecular characteristics, development, evolution, and therapeutic perspectives for pediatric high-grade glioma (pHGG) arising in cerebral hemispheres. Recently, the understanding of biology of pHGG experienced a revolution with discoveries arising from genomic and epigenomic high-throughput profiling techniques. These findings led to identification of prevalent molecular alterations in pHGG and revealed a strong connection between epigenetic dysregulation and pHGG development. Although we are only beginning to unravel the molecular biology underlying pHGG, there is a desperate need to develop therapies that would improve the outcome of pHGG patients, as current therapies do not elicit significant improvement in median survival for this patient population. We explore the molecular and cell biology and clinical state-of-the-art of pediatric high-grade gliomas (pHGGs) arising in cerebral hemispheres. We discuss the role of driving mutations, with a special consideration of the role of epigenetic-disrupting mutations. We will also discuss the possibilities of targeting unique molecular vulnerabilities of hemispherical pHGG to design innovative tailored therapies.

Role of Klotho Protein in Tumor Genesis, Cancer Progression, and Prognosis in Patients with High-Grade Glioma

2019 ◽  
Vol 130 ◽  
pp. e324-e332 ◽  
Author(s):  
Naama Peshes-Yeloz ◽  
Lior Ungar ◽  
Anton Wohl ◽  
Elad Jacoby ◽  
Tamar Fisher ◽  
...  
Keyword(s):  
Cancer Progression ◽  
High Grade Glioma ◽  
High Grade ◽  
Klotho Protein

scholarly journals HG-10 * HYPOXIA PATHWAY DRIVEN BY HIF-1ALPHA ARE PREDOMINANTLY INVOLVED IN PEDIATRIC HIGH GRADE GLIOMA AND REPRESENT PROMISING THERAPEUTIC TARGETS

2015 ◽  
Vol 17 (suppl 3) ◽  
pp. iii12-iii12
Author(s):  
C. Lasthaus ◽  
M. Litzler ◽  
C. Bour ◽  
D. Guenot ◽  
N. Entz-Werle
Keyword(s):  
Therapeutic Targets ◽  
High Grade Glioma ◽  
High Grade ◽  
Pediatric High Grade Glioma

scholarly journals Single-Cell Transcriptomic Analysis Revealed a Critical Role of SPP1/CD44-Mediated Crosstalk Between Macrophages and Cancer Cells in Glioma

2021 ◽  
Vol 9 ◽  
Author(s):  
Cong He ◽  
Luoyan Sheng ◽  
Deshen Pan ◽  
Shuai Jiang ◽  
Li Ding ◽  
...  
Keyword(s):  
Single Cell ◽  
Tumor Heterogeneity ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Cell Communication ◽  
High Grade Glioma ◽  
Sequencing Analysis ◽  
High Grade ◽  
Cellular Components

High-grade glioma is one of the most lethal human cancers characterized by extensive tumor heterogeneity. In order to identify cellular and molecular mechanisms that drive tumor heterogeneity of this lethal disease, we performed single-cell RNA sequencing analysis of one high-grade glioma. Accordingly, we analyzed the individual cellular components in the ecosystem of this tumor. We found that tumor-associated macrophages are predominant in the immune microenvironment. Furthermore, we identified five distinct subpopulations of tumor cells, including one cycling, two OPC/NPC-like and two MES-like cell subpopulations. Moreover, we revealed the evolutionary transition from the cycling to OPC/NPC-like and MES-like cells by trajectory analysis. Importantly, we found that SPP1/CD44 interaction plays a critical role in macrophage-mediated activation of MES-like cells by exploring the cell-cell communication among all cellular components in the tumor ecosystem. Finally, we showed that high expression levels of both SPP1 and CD44 correlate with an increased infiltration of macrophages and poor prognosis of glioma patients. Taken together, this study provided a single-cell atlas of one high-grade glioma and revealed a critical role of macrophage-mediated SPP1/CD44 signaling in glioma progression, indicating that the SPP1/CD44 axis is a potential target for glioma treatment.

scholarly journals HGG-41. STRUCTURAL VARIANT DRIVERS IN PEDIATRIC HIGH-GRADE GLIOMA

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii351-iii351
Author(s):  
Frank Dubois ◽  
Ofer Shapira ◽  
Noah Greenwald ◽  
Travis Zack ◽  
Jessica W Tsai ◽  
...  
Keyword(s):  
Copy Number ◽  
High Grade Glioma ◽  
High Grade ◽  
Structural Variants ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Effector Domains ◽  
Topologically Associating Domains ◽  
Genome Wide ◽  
Pediatric High Grade Glioma

Abstract BACKGROUND Driver single nucleotide variants (SNV) and somatic copy number aberrations (SCNA) of pediatric high-grade glioma (pHGGs), including Diffuse Midline Gliomas (DMGs) are characterized. However, structural variants (SVs) in pHGGs and the mechanisms through which they contribute to glioma formation have not been systematically analyzed genome-wide. METHODS Using SvABA for SVs as well as the latest pipelines for SCNAs and SNVs we analyzed whole-genome sequencing from 174 patients. This includes 60 previously unpublished samples, 43 of which are DMGs. Signature analysis allowed us to define pHGG groups with shared SV characteristics. Significantly recurring SV breakpoints and juxtapositions were identified with algorithms we recently developed and the findings were correlated with RNAseq and H3K27ac ChIPseq. RESULTS The SV characteristics in pHGG showed three groups defined by either complex, intermediate or simple signature activities. These associated with distinct combinations of known driver oncogenes. Our statistical analysis revealed recurring SVs in the topologically associating domains of MYCN, MYC, EGFR, PDGFRA & MET. These correlated with increased mRNA expression and amplification of H3K27ac peaks. Complex recurring amplifications showed characteristics of extrachromosomal amplicons and were enriched in coding SVs splitting protein regulatory from effector domains. Integrative analysis of all SCNAs, SNVs & SVs revealed patterns of characteristic combinations between potential drivers and signatures. This included two distinct groups of H3K27M DMGs with either complex or simple signatures and different combinations of associated variants. CONCLUSION Recurrent SVs associate with signatures shaped by an underlying process, which can lead to distinct mechanisms to activate the same oncogene.

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