bims-malgli Biomed News
on Biology of malignant gliomas
Issue of 2022–10–09
fourteen papers selected by
Oltea Sampetrean, Keio University
  1. Neuropilin-1 modulates the 3D invasive properties of glioblastoma stem-like cells.
  2. The current state of glioma data registries.
  3. Immunotherapy approaches for the treatment of diffuse midline gliomas.
  4. Niche deconvolution of the glioblastoma proteome reveals a distinct infiltrative phenotype within the proneural transcriptomic subgroup.
  5. Ribosome specialization in glioblastoma.
  6. Prognostic value of lactate metabolism-related gene expression signature in adult primary gliomas and its impact on the tumor immune microenvironment.
  7. Detecting monocyte trafficking in an animal model of glioblastoma using R2* and quantitative susceptibility mapping.
  8. Structural connectome quantifies tumour invasion and predicts survival in glioblastoma patients.
  9. T cell receptor dynamic and transcriptional determinants of T cell expansion in glioma-infiltrating T cells.
  10. Alternative RNA splicing modulates ribosomal composition and determines the spatial phenotype of glioblastoma cells.
  11. Inhibition of the pseudokinase MLKL alters extracellular vesicle release and reduces tumor growth in glioblastoma.
  12. Characterizing the biology of primary brain tumors and their microenvironment via single-cell profiling methods.
  13. CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2015-2019.
  14. Molecular and clinicopathologic characteristics of gliomas with EP300::BCOR fusions.
  1. Front Cell Dev Biol. 2022 ;10 981583
    Neuropilin-1 modulates the 3D invasive properties of glioblastoma stem-like cells.
    Mathilde Kerhervé, Sara Rosińska, Kilian Trillet, Alya Zeinaty, Magalie Feyeux, Steven Nedellec, Julie Gavard.
      Glioblastoma multiforme (GBM) is a rare, yet devastating, primary brain tumor in adults. Current treatments remain generally ineffective and GBM almost invariably recurs, resulting in median survival of 15 months. This high malignancy sources notably from the resilience and invasive capabilities of tumor cells. Within GBM, exists a population of self-sustaining transformed cells with stem-like properties (GSCs), which are thought to be responsible for tumor initiation, growth, and invasion, as well as recurrence. In the tumor microenvironment, GSCs might be found in the vicinity of brain endothelial cells, which provide a protective habitat. Likewise, these resistant, quiescent GSCs may accumulate in hypoxic zones, away from the perivascular niche, or travel towards the healthy brain parenchyma, by eminently co-opting neuro-vascular tracks. Herein, we established an ex vivo model to explore GSC invasive behavior. We found that patient-derived cells massively invade the collagen matrix. In addition, we described that the glycoprotein Neuropilin-1 (NRP1) contributes to GSC spreading and invasion. Indeed, both RNA interference-mediated silencing and CRISPR-mediated gene editing deletion of NRP1 strongly impaired the 3D invasive properties of patient-derived GSCs and their close localization to the brain blood vessels. Of note, other typical features of GSCs, such as expansion and self-renewal were maintained. From a mechanistic standpoint, this biological effect might rely on the expression of the β3 subunit integrin cell-extracellular matrix adhesive receptor. Our data, therefore, propose a reliable approach to explore invasive properties of patient glioma cells ex vivo and identify NRP1 as a mediator in this malignant process.
    Keywords:  adhesion; collagen; glioma; integrin; invasion; migration
    DOI:  https://doi.org/10.3389/fcell.2022.981583
  2. Neurooncol Adv. 2022 Jan-Dec;4(1):4(1): vdac099
    The current state of glioma data registries.
    Alexander G Yearley, Julian Bryan Iorgulescu, Ennio Antonio Chiocca, Pier Paolo Peruzzi, Timothy R Smith, David A Reardon, Michael A Mooney.
       Background: The landscape of glioma research has evolved in the past 20 years to include numerous large, multi-institutional, database efforts compiling either clinical data on glioma patients, molecular data on glioma specimens, or a combination of both. While these strategies can provide a wealth of information for glioma research, obtaining information regarding data availability and access specifications can be challenging.
    Methods: We reviewed the literature for ongoing clinical, molecular, and combined database efforts related to glioma research to provide researchers with a curated overview of the current state of glioma database resources.
    Results: We identified and reviewed a total of 20 databases with data collection spanning from 1975 to 2022. Surveyed databases included both low- and high-grade gliomas, and data elements included over 100 clinical variables and 12 molecular data types. Select database strengths included large sample sizes and a wide variety of variables available, while limitations of some databases included complex data access requirements and a lack of glioma-specific variables.
    Conclusions: This review highlights current databases and registries and their potential utility in clinical and genomic glioma research. While many high-quality resources exist, the fluid nature of glioma taxonomy makes it difficult to isolate a large cohort of patients with a pathologically confirmed diagnosis. Large, well-defined, and publicly available glioma datasets have the potential to expand the reach of glioma research and drive the field forward.
    Keywords:  clinical research; database; glioblastoma; glioma; registry
    DOI:  https://doi.org/10.1093/noajnl/vdac099
  3. Oncoimmunology. 2022 ;11(1): 2124058
    Immunotherapy approaches for the treatment of diffuse midline gliomas.
    Joshua D Bernstock, Samantha E Hoffman, Ari D Kappel, Pablo A Valdes, Walid Ibn Essayed, Neil V Klinger, Kyung-Don Kang, Stacie K Totsch, Hannah E Olsen, Charles W Schlappi, Katharina Filipski, Florian A Gessler, Lissa Baird, Mariella G Filbin, Rintaro Hashizume, Oren J Becher, Gregory K Friedman.
      Diffuse midline gliomas (DMG) are a highly aggressive and universally fatal subgroup of pediatric tumors responsible for the majority of childhood brain tumor deaths. Median overall survival is less than 12 months with a 90% mortality rate at 2 years from diagnosis. Research into the underlying tumor biology and numerous clinical trials have done little to change the invariably poor prognosis. Continued development of novel, efficacious therapeutic options for DMGs remains a critically important area of active investigation. Given that DMGs are not amenable to surgical resection, have only limited response to radiation, and are refractory to traditional chemotherapy, immunotherapy has emerged as a promising alternative treatment modality. This review summarizes the various immunotherapy-based treatments for DMG as well as their specific limitations. We explore the use of cell-based therapies, oncolytic virotherapy or immunovirotherapy, immune checkpoint inhibition, and immunomodulatory vaccination strategies, and highlight the recent clinical success of anti-GD2 CAR-T therapy in diffuse intrinsic pontine glioma (DIPG) patients. Finally, we address the challenges faced in translating preclinical and early phase clinical trial data into effective standardized treatment for DMG patients.
    Keywords:  Virotherapy; cell-based therapy; diffuse intrinsic pontine glioma (DIPG); diffuse midline gliomas (DMG); glioma; immune checkpoint inhibition (ICI); immunotherapy; pediatric neuro-oncology; pediatric neurosurgery; vaccination
    DOI:  https://doi.org/10.1080/2162402X.2022.2124058
  4. Sci Data. 2022 Oct 01. 9(1): 596
    Niche deconvolution of the glioblastoma proteome reveals a distinct infiltrative phenotype within the proneural transcriptomic subgroup.
    K H Brian Lam, Phedias Diamandis.
      Glioblastoma is often subdivided into three transcriptional subtypes (classical, proneural, mesenchymal) based on bulk RNA signatures that correlate with distinct genetic and clinical features. Potential cellular-level differences of these subgroups, such as the relative proportions of glioblastoma's hallmark histopathologic features (e.g. brain infiltration, microvascular proliferation), may provide insight into their distinct phenotypes but are, however, not well understood. Here we leverage machine learning and reference proteomic profiles derived from micro-dissected samples of these major histomorphologic glioblastoma features to deconvolute and estimate niche proportions in an independent proteogenomically-characterized cohort. This approach revealed a strong association of the proneural transcriptional subtype with a diffusely infiltrating phenotype. Similarly, enrichment of a microvascular proliferation proteomic signature was seen within the mesenchymal subtype. This study is the first to link differences in the cellular pathology signatures and transcriptional profiles of glioblastoma, providing potential new insights into the genetic drivers and poor treatment response of specific subsets of glioblastomas.
    DOI:  https://doi.org/10.1038/s41597-022-01716-5
  5. Nat Cell Biol. 2022 Oct 03.
    Ribosome specialization in glioblastoma.
    Naomi R Genuth, Maria Barna.
      
    DOI:  https://doi.org/10.1038/s41556-022-01000-z
  6. Front Oncol. 2022 ;12 1008219
    Prognostic value of lactate metabolism-related gene expression signature in adult primary gliomas and its impact on the tumor immune microenvironment.
    Zhihao Wang, Shuxin Zhang, Junhong Li, Yunbo Yuan, Siliang Chen, Mingrong Zuo, Wenhao Li, Wentao Feng, Mina Chen, Yanhui Liu.
      Glioma is one of the most malignant intracerebral tumors, whose treatment means was limited, and prognosis was unsatisfactory. Lactate metabolism patterns have been shown to be highly heterogenous among different tumors and produce diverse impact on the tumor microenvironment. To understand the characteristics and implications of lactate metabolism gene expression, we developed a lactate metabolism-related gene expression signature of gliomas based on RNA-sequencing data of a total of 965 patient samples from TCGA, CGGA, and our own glioma cohort. Sixty-three lactate metabolism-related genes (LMGs) were differentially expressed between glioma and normal brain tissue, and consensus clustering analysis identified two clusters distinct LMG expression patterns. The consensus clusters differed in prognosis, molecular characteristics and estimated immune microenvironment landscape involving immune checkpoint proteins, T cell dysfunction and exclusion, as well as tumor purity. Univariate Cox regression and Least Absolute Shrinkage and Selection Operator (LASSO) Cox hazard regression was applied in determining of prognosis-related lactate metabolism genes (PRLMGs), on which prognostic lactate metabolism risk score (PLMRS) was constructed. The high PLMRS group was associated with significantly poorer patient outcome. A nomogram containing PLMRS and other independent prognostic variables was established with remarkable predictive performance on patient survival. Exploration on the somatic mutations and copy number variations of the high- and low-PLMRS groups demonstrated their distinct genetic background. Together, our results indicated that the expression signature of LMG was associated with the prognosis of glioma patients and influenced the activity of immune cells in the tumor microenvironment, which may serve as a potential biomarker for predicting response of gliomas to immunotherapy.
    Keywords:  glioma; immunity; lactate metabolism; prognosis; tumor microenvironment
    DOI:  https://doi.org/10.3389/fonc.2022.1008219
  7. Cancer Immunol Immunother. 2022 Oct 04.
    Detecting monocyte trafficking in an animal model of glioblastoma using R2* and quantitative susceptibility mapping.
    Runze Yang, A Max Hamilton, Hongfu Sun, Khalil S Rawji, Susobhan Sarkar, Reza Mirzaei, G Bruce Pike, V Wee Yong, Jeff F Dunn.
       BACKGROUND: The role of tumor-associated macrophages (TAMs) in glioblastoma (GBM) disease progression has received increasing attention. Recent advances have shown that TAMs can be re-programmed to exert a pro-inflammatory, anti-tumor effect to control GBMs. However, imaging methods capable of differentiating tumor progression from immunotherapy treatment effects have been lacking, making timely assessment of treatment response difficult. We showed that tracking monocytes using iron oxide nanoparticle (USPIO) with MRI can be a sensitive imaging method to detect therapy response directed at the innate immune system.
    METHODS: We implanted syngeneic mouse glioma stem cells into C57/BL6 mice and treated the animals with either niacin (a stimulator of innate immunity) or vehicle. Animals were imaged using an anatomical MRI sequence, R2* mapping, and quantitative susceptibility mapping (QSM) before and after USPIO injection.
    RESULTS: Compared to vehicles, niacin-treated animals showed significantly higher susceptibility and R2*, representing USPIO and monocyte infiltration into the tumor. We observed a significant reduction in tumor size in the niacin-treated group 7 days later. We validated our MRI results with flow cytometry and immunofluoresence, which showed that niacin decreased pro-inflammatory Ly6C high monocytes in the blood but increased CD16/32 pro-inflammatory macrophages within the tumor, consistent with migration of these pro-inflammatory innate immune cells from the blood to the tumor.
    CONCLUSION: MRI with USPIO injection can detect therapeutic responses of innate immune stimulating agents before changes in tumor size have occurred, providing a potential complementary imaging technique to monitor cancer immunotherapies.
    MANUSCRIPT HIGHLIGHT: We show that iron oxide nanoparticles (USPIOs) can be used to label innate immune cells and detect the trafficking of pro-inflammatory monocytes into the glioblastoma. This preceded changes in tumor size, making it a more sensitive imaging technique.
    Keywords:  Cell tracking; Glioblastoma; Immunotherapy; Iron oxide; MRI
    DOI:  https://doi.org/10.1007/s00262-022-03297-z
  8. Brain. 2022 Oct 03. pii: awac360. [Epub ahead of print]
    Structural connectome quantifies tumour invasion and predicts survival in glioblastoma patients.
    Yiran Wei, Chao Li, Zaixu Cui, Roxanne Claudeve Mayrand, Jingjing Zou, Adrianna Leanne Kok Chi Wong, Rohitashwa Sinha, Tomasz Matys, Carola Bibiane Schönlieb, Stephen John Price.
      Glioblastoma is characterised by diffuse infiltration into the surrounding tissue along white matter tracts. Identifying the invisible tumour invasion beyond focal lesion promises more effective treatment, which remains a significant challenge. It is increasingly accepted that glioblastoma could widely affect brain structure and function, and further lead to reorganisation of neural connectivity. Quantifying neural connectivity in glioblastoma may provide a valuable tool for identifying tumour invasion. Here we propose an approach to systematically identify tumour invasion by quantifying the structural connectome in glioblastoma patients. We first recruit two independent prospective glioblastoma cohorts: Discovery cohort with 117 patients and Validation cohort with 42 patients. Next, we employ diffusion MRI of healthy subjects to construct tractography templates indicating white matter connection pathways between brain regions. Next, we construct fractional anisotropy skeletons from diffusion MRI using an improved voxel projection approach based on the tract-based spatial statistics, where the strengths of white matter connection and brain regions are estimated. To quantify the disrupted connectome, we calculate the deviation of the connectome strengths of patients from that of the age-matched healthy controls. We then categorise the disruption into regional disruptions based on the relative location of connectome to focal lesions. We also characterise the topological properties of the patient connectome based on the graph theory. Finally, we investigate the clinical, cognitive and prognostic significance of connectome metrics using Pearson correlation test, mediation test and survival models. Our results show that the connectome disruptions in glioblastoma patients are widespread in the normal-appearing brain beyond focal lesions, associated with lower pre-operative performance (P < 0.001), impaired cognitive function (P < 0.001), and worse survival (overall survival: hazard ratio = 1.46, P = 0.049; progression-free survival: hazard ratio = 1.49, P = 0.019). Additionally, these distant disruptions mediate the effect on topological alterations of the connectome (mediation effect: clustering coefficient: -0.017, P < 0.001, characteristic path length: 0.17, P = 0.008). Further, the preserved connectome in the normal-appearing brain demonstrates evidence of connectivity reorganisation, where the increased neural connectivity is associated with better overall survival (log-rank P = 0.005). In conclusion, our connectome approach could reveal and quantify the glioblastoma invasion distant from the focal lesion and invisible on the conventional MRI. The structural disruptions in the normal-appearing brain were associated with the topological alteration of the brain and could indicate treatment target. Our approach promises to aid more accurate patient stratification and more precise treatment planning.
    Keywords:  brain connectome; brain reorganisation; glioblastoma; survival analysis; tumour invasion
    DOI:  https://doi.org/10.1093/brain/awac360
  9. Neurooncol Adv. 2022 Jan-Dec;4(1):4(1): vdac140
    T cell receptor dynamic and transcriptional determinants of T cell expansion in glioma-infiltrating T cells.
    Kevin Hai-Ning Lu, Julius Michel, Michael Kilian, Katrin Aslan, Hao Qi, Niklas Kehl, Stefanie Jung, Khwab Sanghvi, Katharina Lindner, Xin-Wen Zhang, Edward W Green, Isabel Poschke, Miriam Ratliff, Theresa Bunse, Felix Sahm, Andreas von Deimling, Wolfgang Wick, Michael Platten, Lukas Bunse.
       Background: Glioblastoma (GBM) is characterized by low numbers of glioma-infiltrating lymphocytes (GIL) with a dysfunctional phenotype. Whether this dysfunctional phenotype is fixed or can be reversed upon ex vivo culturing is poorly understood. The aim of this study was to assess T cell receptor (TCR)-dynamics and -specificities as well as determinants of in vitro GIL expansion by sequencing-based technologies and functional assays to explore the use of GIL for cell therapy.
    Methods: By means of flow cytometry, T cell functionality in GIL cultures was assessed from 9 GBM patients. TCR beta sequencing (TCRB-seq) was used for TCR repertoire profiling before and after in vitro expansion. Microarrays or RNA sequencing (RNA-seq) were performed from 6 micro-dissected GBM tissues and healthy brain RNA to assess the individual expression of GBM-associated antigens (GAA). GIL reactivity against in silico predicted tumor-associated antigens (TAA) and patient-individual GAA was assessed by ELISpot assay. Combined ex vivo single cell (sc)TCR-/RNA-seq and post-expansion TCRB-seq were used to evaluate transcriptional signatures that determine GIL expansion.
    Results: Human GIL regains cellular fitness upon in vitro expansion. Profound TCR dynamics were observed during in vitro expansion and only in one of six GIL cultures, reactivity against GAA was observed. Paired ex vivo scTCR/RNA-seq and TCRB-seq revealed predictive transcriptional signatures that determine GIL expansion.
    Conclusions: Profound TCR repertoire dynamics occur during GIL expansion. Ex vivo transcriptional T cell states determine expansion capacity in gliomas. Our observation has important implications for the use of GIL for cell therapy including genetic manipulation to maintain both antigen specificity and expansion capacity.
    Keywords:  TCR repertoire; TCR-seq; cellular immunotherapy; glioma; glioma-infiltrating lymphocytes
    DOI:  https://doi.org/10.1093/noajnl/vdac140
  10. Nat Cell Biol. 2022 Oct 03.
    Alternative RNA splicing modulates ribosomal composition and determines the spatial phenotype of glioblastoma cells.
    Tatyana D Larionova, Soniya Bastola, Tatiana E Aksinina, Ksenia S Anufrieva, Jia Wang, Victoria O Shender, Dmitriy E Andreev, Tatiana F Kovalenko, Georgij P Arapidi, Polina V Shnaider, Anastasia N Kazakova, Yaroslav A Latyshev, Victor V Tatarskiy, Alexander A Shtil, Pascale Moreau, Francis Giraud, Chaoxi Li, Yichan Wang, Maria P Rubtsova, Olga A Dontsova, Michael Condro, Benjamin M Ellingson, Mikhail I Shakhparonov, Harley I Kornblum, Ichiro Nakano, Marat S Pavlyukov.
      Glioblastoma (GBM) is characterized by exceptionally high intratumoral heterogeneity. However, the molecular mechanisms underlying the origin of different GBM cell populations remain unclear. Here, we found that the compositions of ribosomes of GBM cells in the tumour core and edge differ due to alternative RNA splicing. The acidic pH in the core switches before messenger RNA splicing of the ribosomal gene RPL22L1 towards the RPL22L1b isoform. This allows cells to survive acidosis, increases stemness and correlates with worse patient outcome. Mechanistically, RPL22L1b promotes RNA splicing by interacting with lncMALAT1 in the nucleus and inducing its degradation. Contrarily, in the tumour edge region, RPL22L1a interacts with ribosomes in the cytoplasm and upregulates the translation of multiple messenger RNAs including TP53. We found that the RPL22L1 isoform switch is regulated by SRSF4 and identified a compound that inhibits this process and decreases tumour growth. These findings demonstrate how distinct GBM cell populations arise during tumour growth. Targeting this mechanism may decrease GBM heterogeneity and facilitate therapy.
    DOI:  https://doi.org/10.1038/s41556-022-00994-w
  11. iScience. 2022 Oct 21. 25(10): 105118
    Inhibition of the pseudokinase MLKL alters extracellular vesicle release and reduces tumor growth in glioblastoma.
    Gwennan André-Grégoire, Clément Maghe, Tiphaine Douanne, Sara Rosińska, Fiorella Spinelli, An Thys, Kilian Trillet, Kathryn A Jacobs, Cyndie Ballu, Aurélien Dupont, Anne-Marie Lyne, Florence M G Cavalli, Ignacio Busnelli, Vincent Hyenne, Jacky G Goetz, Nicolas Bidère, Julie Gavard.
      Extracellular vesicles (EVs) are lipid-based nanosized particles that convey biological material from donor to recipient cells. EVs play key roles in glioblastoma progression because glioblastoma stem-like cells (GSCs) release pro-oncogenic, pro-angiogenic, and pro-inflammatory EVs. However, the molecular basis of EV release remains poorly understood. Here, we report the identification of the pseudokinase MLKL, a crucial effector of cell death by necroptosis, as a regulator of the constitutive secretion of EVs in GSCs. We find that genetic, protein, and pharmacological targeting of MLKL alters intracellular trafficking and EV release, and reduces GSC expansion. Nevertheless, this function ascribed to MLKL appears independent of its role during necroptosis. In vivo, pharmacological inhibition of MLKL reduces the tumor burden and the level of plasmatic EVs. This work highlights the necroptosis-independent role of MLKL in vesicle release and suggests that interfering with EVs is a promising therapeutic option to sensitize glioblastoma cells.
    Keywords:  Cancer; Cell biology; Functional aspects of cell biology
    DOI:  https://doi.org/10.1016/j.isci.2022.105118
  12. Neuro Oncol. 2022 Oct 05. pii: noac211. [Epub ahead of print]
    Characterizing the biology of primary brain tumors and their microenvironment via single-cell profiling methods.
    L Nicolas Gonzalez Castro, Ilon Liu, Mariella Filbin.
      Genomic and transcriptional heterogeneity is prevalent among the most common and aggressive primary brain tumors in children and adults. Over the past 20 years, advances in bioengineering, biochemistry and bioinformatics have enabled the development of an array of techniques to study tumor biology at single-cell resolution. The application of these techniques to study primary brain tumors has helped advance our understanding of their intra-tumoral heterogeneity and uncover new insights regarding their co-option of developmental programs and signaling from their microenvironment to promote tumor proliferation and invasion. These insights are currently being harnessed to develop new therapeutic approaches. Here we provide an overview of current single-cell techniques and discuss relevant biology and therapeutic insights uncovered by their application to primary brain tumors in children and adults.
    Keywords:  gliomas; medulloblastoma; single-cell methods; single-cell multi-omics; singlecell RNA-seq
    DOI:  https://doi.org/10.1093/neuonc/noac211
  13. Neuro Oncol. 2022 Oct 05. 24(Supplement_5): v1-v95
    CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2015-2019.
    Quinn T Ostrom, Mackenzie Price, Corey Neff, Gino Cioffi, Kristin A Waite, Carol Kruchko, Jill S Barnholtz-Sloan.
      The Central Brain Tumor Registry of the United States (CBTRUS), in collaboration with the Centers for Disease Control and Prevention and the National Cancer Institute, is the largest population-based registry focused exclusively on primary brain and other central nervous system (CNS) tumors in the United States (US) and represents the entire US population. This report contains the most up-to-date population-based data on primary brain tumors available and supersedes all previous reports in terms of completeness and accuracy. All rates are age-adjusted using the 2000 US standard population and presented per 100,000 population. The average annual age-adjusted incidence rate (AAAIR) of all malignant and non-malignant brain and other CNS tumors was 24.71 per 100,000 population (malignant AAAIR=7.02 and non-malignant AAAIR=17.69). This overall rate was higher in females compared to males (27.62 versus 21.60 per 100,000) and non-Hispanic persons compared to Hispanic persons (25.09 versus 22.95 per 100,000). The most commonly occurring malignant brain and other CNS histopathology was glioblastoma (14.2% of all tumors and 50.1% of all malignant tumors), and the most common non-malignant histopathology was meningioma (39.7% of all tumors and 55.4% of all non-malignant tumors). Glioblastoma was more common in males, and meningiomas were more common in females. In children and adolescents (ages 0-19 years), the incidence rate of all primary brain and other CNS tumors was 6.20 per 100,000 population. An estimated 93,470 new cases of malignant and non-malignant brain and other CNS tumors are expected to be diagnosed in the US population in 2022 (26,670 malignant and 66,806 non-malignant). There were 84,264 deaths attributed to malignant brain and other CNS tumors between 2015 and 2019. This represents an average annual mortality rate of 4.41 per 100,000 population and an average of 16,853 deaths per year. The five-year relative survival rate following diagnosis of a malignant brain and other CNS tumor was 35.7%, while for non-malignant brain and other CNS tumors the five-year relative survival rate was 91.8%.
    DOI:  https://doi.org/10.1093/neuonc/noac202
  14. Acta Neuropathol. 2022 Oct 06.
    Molecular and clinicopathologic characteristics of gliomas with EP300::BCOR fusions.
    Zhichao Wu, Sharika Rajan, Hye-Jung Chung, Mark Raffeld, Pavalan Panneer Selvam, Leonille Schweizer, Arie Perry, David Samuel, Caterina Giannini, Aditya Ragunathan, Matthew P Frosch, Michael S Marshall, Daniel R Boué, Kliment Donev, Stewart G Neill, Igor Fernandes, Adam Resnick, Brian Rood, Thomas J Cummings, Anne F Buckley, Linda Szymanski, Osorio Lopes Abath Neto, Leor Zach, Howard Colman, Samuel Cheshier, Jennifer Ziskin, Manoj Tyagi, David Capper, Zied Abdullaev, Patrick J Cimino, Martha Quezado, Drew Pratt, Kenneth Aldape.
      
    DOI:  https://doi.org/10.1007/s00401-022-02508-2
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