259 results match your criteria glioblastomas harbor

Glioblastomas with primitive neuronal component harbor a distinct methylation and copy-number profile with inactivation of TP53, PTEN, and RB1.

Acta Neuropathol 2021 Apr 19. Epub 2021 Apr 19.

Division of Neuropathology, Institute of Pathology, Basel University Hospital, Basel, Switzerland.

Glioblastoma IDH-wildtype presents with a wide histological spectrum. Some features are so distinctive that they are considered as separate histological variants or patterns for the purpose of classification. However, these usually lack defined (epi-)genetic alterations or profiles correlating with this histology. Read More

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A Voxel-Based Radiographic Analysis Reveals the Biological Character of Proneural-Mesenchymal Transition in Glioblastoma.

Front Oncol 2021 17;11:595259. Epub 2021 Mar 17.

Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.

Proneural and mesenchymal subtypes are the most distinct demarcated categories in classification scheme, and there is often a shift from proneural type to mesenchymal subtype in the progression of glioblastoma (GBM). The molecular characters are determined by specific genomic methods, however, the application of radiography in clinical practice remains to be further studied. Here, we studied the topography features of GBM in proneural subtype, and further demonstrated the survival characteristics and proneural-mesenchymal transition (PMT) progression of samples by combining with the imaging variables. Read More

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Radiotherapy versus combination radiotherapy-bevacizumab for the treatment of recurrent high-grade glioma: a systematic review.

Acta Neurochir (Wien) 2021 Apr 2. Epub 2021 Apr 2.

Departments of Neurosurgery, University of California, Los Angeles, 300 Stein Plaza, Suite 562, Los Angeles, CA, USA.

Background: High-grade gliomas (HGG) comprise the most common primary adult brain cancers and universally recur. Combination of re-irradiation therapy (reRT) and bevacizumab (BVZ) therapy for recurrent HGG is common, but its reported efficacy is mixed.

Objective: To assess clinical outcomes after reRT ± BVZ in recurrent HGG patients receiving stereotactic radiosurgery (SRS), hypofractionated radiosurgery (HFSRT), or fully fractionated radiotherapy (FFRT). Read More

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NVP-BEZ235 or JAKi Treatment leads to decreased survival of examined GBM and BBC cells.

Cancer Treat Res Commun 2021 Feb 17;27:100340. Epub 2021 Feb 17.

Department of Biology, University of Texas- Rio Grande Valley, 1201 W. University Dr., Edinburg, TX 78539, United States. Electronic address:

Cancer cells almost universally harbor constitutively active Phosphatidylinositol-3 Kinase (PI3K) Pathway activity via mutation of key signaling components and/or epigenetic mechanisms. Scores of PI3K Pathway inhibitors are currently under investigation as putative chemotherapeutics. However, feedback and stem cell mechanisms induced by PI3K Pathway inhibition can lead to reduced treatment efficacy. Read More

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February 2021

Diffuse Gliomas of the Brainstem and Cerebellum in Adults Show Molecular Heterogeneity.

Am J Surg Pathol 2021 Feb 16. Epub 2021 Feb 16.

Departments of Laboratory Medicine and Pathology Radiology Neurology Neurologic Surgery Medical Oncology Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN.

Posterior fossa (PF) diffuse gliomas in pediatric patients frequently harbor the H3 K27M mutation. Among adults, PF diffuse gliomas are rare, with limited data regarding molecular features and clinical outcomes. We identified 28 adult PF diffuse glioma patients (17 males; median: 50 y, range: 19 to 78 y), with surgery performed at our institution (13 brainstem; 15 cerebellum). Read More

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February 2021

Single-cell chromatin accessibility profiling of glioblastoma identifies an invasive cancer stem cell population associated with lower survival.

Elife 2021 Jan 11;10. Epub 2021 Jan 11.

Princess Margaret Cancer Centre, University Health Network, Toronto, Canada.

Chromatin accessibility discriminates stem from mature cell populations, enabling the identification of primitive stem-like cells in primary tumors, such as glioblastoma (GBM) where self-renewing cells driving cancer progression and recurrence are prime targets for therapeutic intervention. We show, using single-cell chromatin accessibility, that primary human GBMs harbor a heterogeneous self-renewing population whose diversity is captured in patient-derived glioblastoma stem cells (GSCs). In-depth characterization of chromatin accessibility in GSCs identifies three GSC states: Reactive, Constructive, and Invasive, each governed by uniquely essential transcription factors and present within GBMs in varying proportions. Read More

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January 2021

To Become or Not to Become Tumorigenic: Subventricular Zone Hippocampal Neural Stem Cells.

Front Oncol 2020 27;10:602217. Epub 2020 Nov 27.

Departamento de Fisiología, Facultad de Biología, Universidad de Sevilla, Seville, Spain.

Neural stem cells (NSCs) persist in the adult mammalian brain in two neurogenic regions: the subventricular zone lining the lateral ventricles and the dentate gyrus of the hippocampus. Compelling evidence suggests that NSCs of the subventricular zone could be the cell type of origin of glioblastoma, the most devastating brain tumor. Studies in glioblastoma patients revealed that NSCs of the tumor-free subventricular zone, harbor cancer-driver mutations that were found in the tumor cells but were not present in normal cortical tissue. Read More

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November 2020

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

Acta Neuropathol Commun 2020 11 9;8(1):186. Epub 2020 Nov 9.

Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.

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. Read More

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November 2020

A cell-penetrating MARCKS mimetic selectively triggers cytolytic death in glioblastoma.

Oncogene 2020 11 19;39(46):6961-6974. Epub 2020 Oct 19.

Department of Radiation Oncology, The University of Alabama at Birmingham, Birmingham, AL, USA.

Glioblastoma (GBM) is an aggressive malignancy with limited effectiveness of standard of care therapies including surgery, radiation, and temozolomide chemotherapy necessitating novel therapeutics. Unfortunately, GBMs also harbor several signaling alterations that protect them from traditional therapies that rely on apoptotic programmed cell death. Because almost all GBM tumors have dysregulated phosphoinositide signaling as part of that process, we hypothesized that peptide mimetics derived from the phospholipid binding domain of Myristoylated alanine-rich C-kinase substrate (MARCKS) could serve as a novel GBM therapeutic. Read More

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November 2020

IDH-mutant gliomas harbor fewer regulatory T cells in humans and mice.

Oncoimmunology 2020 08 20;9(1):1806662. Epub 2020 Aug 20.

Translational Brain Tumor Immunology Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

The metabolic gene isocitrate dehydrogenase 1 () is commonly mutated in lower grade glioma (LGG) and secondary glioblastoma (GBM). Regulatory T cells (Tregs) play a significant role in the suppression of antitumor immunity in human glioma. Given the importance of Tregs in the overall framework of designing immune-based therapies, a better understanding on their association with IDH mutational status remains of critical clinical importance. Read More

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CCAAT/Enhancer-Binding Protein Delta (C/EBPδ): A Previously Unrecognized Tumor Suppressor that Limits the Oncogenic Potential of Pancreatic Ductal Adenocarcinoma Cells.

Cancers (Basel) 2020 Sep 7;12(9). Epub 2020 Sep 7.

Laboratory for Experimental Oncology and Radiobiology, Center for Experimental and Molecular Medicine, Amsterdam University Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.

CCAAT/enhancer-binding protein δ (C/EBPδ) is a transcription factor involved in growth arrest and differentiation, which has consequently been suggested to harbor tumor suppressive activities. However, C/EBPδ over-expression correlates with poor prognosis in glioblastoma and promotes genomic instability in cervical cancer, hinting at an oncogenic role of C/EBPδ in these contexts. Here, we explore the role of C/EBPδ in pancreatic cancer. Read More

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September 2020

Clinical characterization, genetic profiling, and immune infiltration of TOX in diffuse gliomas.

J Transl Med 2020 08 6;18(1):305. Epub 2020 Aug 6.

Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, People's Republic of China.

Background: Immunotherapies targeting glioblastoma (GBM) have led to significant improvements in patient outcomes. TOX is closely associated with the immune environment surrounding tumors, but its role in gliomas is not fully understood.

Methods: Using data from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA), we analyzed the transcriptomes of 1691 WHO grade I-IV human glioma samples. Read More

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Epigenetic Targeting of Mcl-1 Is Synthetically Lethal with Bcl-xL/Bcl-2 Inhibition in Model Systems of Glioblastoma.

Cancers (Basel) 2020 Aug 1;12(8). Epub 2020 Aug 1.

Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032, USA.

Apoptotic resistance remains a hallmark of glioblastoma (GBM), the most common primary brain tumor in adults, and a better understanding of this process may result in more efficient treatments. By utilizing chromatin immunoprecipitation with next-generation sequencing (CHIP-seq), we discovered that GBMs harbor a super enhancer around the Mcl-1 locus, a gene that has been known to confer cell death resistance in GBM. We utilized THZ1, a known super-enhancer blocker, and BH3-mimetics, including ABT263, WEHI-539, and ABT199. Read More

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Involvement of Integrin-Activating Peptides Derived from Tenascin-C in Cancer Aggression and New Anticancer Strategy Using the Fibronectin-Derived Integrin-Inactivating Peptide.

Molecules 2020 Jul 16;25(14). Epub 2020 Jul 16.

Department of Molecular Patho-Physiology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.

Matricellular proteins, which exist in association with the extracellular matrix (ECM) and ECM protein molecules, harbor functional sites within their molecular structures. These functional sites are released through proteolytic cleavage by inflammatory proteinases, such as matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS), and the peptides containing these functional sites have unique biological activities that are often not detected in the parent molecules. We previously showed that tenascin-C (TNC) and plasma fibronectin (pFN), examples of matricellular proteins, have cryptic bioactive sites that have opposite effects on cell adhesion to the ECM. Read More

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Epithelioid glioblastoma with microglia features: potential for novel therapy.

Brain Pathol 2020 11 6;30(6):1119-1133. Epub 2020 Aug 6.

Department of Surgical Pathology, Hyogo College of Medicine, Nishinomiya, Japan.

Epithelioid glioblastoma (E-GBM) was recently designated as a subtype of glioblastoma (GBM) by the World Health Organization (2016). E-GBM is an aggressive and rare variant of GBM that primarily occurs in children and young adults. Although most characterized cases of E-GBM harbor a mutation of the BRAF gene in which valine (V) is substituted by glutamic acid (E) at amino acid 600 (BRAF-V600E), in addition to telomerase reverse transcriptase promoter mutations and homozygous CDKN2A/B deletions, the origins and cellular nature of E-GBM remain uncertain. Read More

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November 2020

Genome-wide analysis of high-risk primary brain cancer pedigrees identifies PDXDC1 as a candidate brain cancer predisposition gene.

Neuro Oncol 2021 02;23(2):277-283

Tel-Aviv Sourasky Medical Center, Tel-Aviv University, Tel-Aviv, Israel.

Background: There is evidence for an inherited contribution to primary brain cancer. Linkage analysis of high-risk brain cancer pedigrees has identified candidate regions of interest in which brain cancer predisposition genes are likely to reside.

Methods: Genome-wide linkage analysis was performed in a unique set of 11 informative, extended, high-risk primary brain cancer pedigrees identified in a population genealogy database, which include from 2 to 6 sampled, related primary brain cancer cases. Read More

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February 2021

Advances in histone deacetylase inhibitors in targeting glioblastoma stem cells.

Cancer Chemother Pharmacol 2020 08 7;86(2):165-179. Epub 2020 Jul 7.

CSIR-Centre for Cellular and Molecular Biology, Habsiguda, Uppal Road, Hyderabad, 500007, Telangana, India.

Glioblastoma multiforme (GBM) is a lethal grade IV glioma (WHO classification) and widely prevalent primary brain tumor in adults. GBM tumors harbor cellular heterogeneity with the presence of a small subpopulation of tumor cells, described as GBM cancer stem cells (CSCs) that pose resistance to standard anticancer regimens and eventually mediate aggressive relapse or intractable progressive GBM. Existing conventional anticancer therapies for GBM do not target GBM stem cells and are mostly palliative; therefore, exploration of new strategies to target stem cells of GBM has to be prioritized for the development of effective GBM therapy. Read More

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Pulsed Reduced Dose Rate Radiotherapy in Conjunction With Bevacizumab or Bevacizumab Alone in Recurrent High-grade Glioma: Survival Outcomes.

Int J Radiat Oncol Biol Phys 2020 11 27;108(4):979-986. Epub 2020 Jun 27.

Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin.

Purpose: Dismal prognosis and limited treatment options for recurrent high-grade glioma have provoked interest in various forms of reirradiation. Pulsed reduced dose rate radiation therapy (pRDR) is a promising technique that exploits low-dose hyper-radiosensitivity of proliferating tumor cells while sparing adjacent nonproliferating normal brain tissue. Large radiation treatment volumes can thus be used to target both contrast-enhancing and FLAIR abnormalities thought to harbor recurrent gross and microscopic disease, respectively. Read More

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November 2020

Assessment of circulating tumor DNA in cerebrospinal fluid by whole exome sequencing to detect genomic alterations of glioblastoma.

Chin Med J (Engl) 2020 Jun;133(12):1415-1421

Department of Neurosurgery/Neuro-Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, China.

Background: Cerebrospinal fluid (CSF) has been demonstrated as a better source of circulating tumor DNA (ctDNA) than plasma for brain tumors. However, it is unclear whether whole exome sequencing (WES) is qualified for detection of ctDNA in CSF. The aim of this study was to determine if assessment of ctDNA in CSF by WES is a feasible approach to detect genomic alterations of glioblastoma. Read More

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5-Aminolevulinic Acid-Guided Surgery for Recurrent Supratentorial Pediatric Neoplasms.

World Neurosurg 2020 09 9;141:e763-e769. Epub 2020 Jun 9.

Department of Neurosurgery, University of the Witwatersrand, Johannesburg and Department of Paediatric Neurosurgery, Nelson Mandela Children's Hospital, Johannesburg, South Africa. Electronic address:

Background: The use of 5-aminolevulinic acid (5-ALA) in pediatric neuro-oncology is considered off-label, and little data are available on its use in tumor recurrence surgery. Here we present our experience with 5-ALA fluorescence-guided surgery for recurrent supratentorial tumors in the pediatric population.

Methods: Eleven pediatric patients presenting with recurrence of a supratentorial high-grade malignancy (5 glioblastoma [GBM], 6 non-GBM) underwent 5-ALA-assisted surgery. Read More

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September 2020

Molecular characteristics and clinical features of multifocal glioblastoma.

J Neurooncol 2020 Jun 21;148(2):389-397. Epub 2020 May 21.

Vivian L. Smith Department of Neurosurgery, The University of Texas Health Science Center at Houston, Houston, TX, USA.

Introduction: Glioblastomas (GBMs) usually occur as a solitary lesion; however, about 0.5-35% present with multiple lesions (M-GBM). The genetic landscape of GBMs have been thoroughly investigated; nevertheless, differences between M-GBM and single-foci GBM (S-GBM) remains unclear. Read More

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Diffusion MRI changes in the anterior subventricular zone following chemoradiation in glioblastoma with posterior ventricular involvement.

J Neurooncol 2020 May 1;147(3):643-652. Epub 2020 Apr 1.

UCLA Brain Tumor Imaging Laboratory (BTIL), Center for Computer Vision and Imaging Biomarkers, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.

Introduction: There is growing evidence that the subventricular zone (SVZ) plays a key role in glioblastoma (GBM) tumorigenesis. However, little is known regarding how the SVZ, which is a harbor for adult neural stem cells, may be influenced by chemoradiation. The current diffusion-weighted imaging (DWI) study explored ipsilateral and contralateral alterations in the anterior SVZ in GBM patients with posterior enhancing lesions following chemoradiation. Read More

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Tumor-derived exosomes in the regulation of macrophage polarization.

Inflamm Res 2020 May 11;69(5):435-451. Epub 2020 Mar 11.

Department of Pharmacology, The University of Illinois at Chicago, Chicago, IL, 60612, USA.

Background: This review focuses on exosomes derived from various cancer cells. The review discusses the possibility of differentiating macrophages in alternatively activated anti-inflammatory pro-tumorigenic M2 macrophage phenotypes and classically activated pro-inflammatory, anti-tumorigenic M1 macrophage phenotypes in the tumor microenvironment (TME). The review is divided into two main parts, as follows: (1) role of exosomes in alternatively activating M2-like macrophages-breast cancer-derived exosomes, hepatocellular carcinoma (HCC) cell-derived exosomes, lung cancer-derived exosomes, prostate cancer-derived exosomes, Oral squamous cell carcinoma (OSCC)-derived exosomes, epithelial ovarian cancer (EOC)-derived exosomes, Glioblastoma (GBM) cell-derived exosomes, and colorectal cancer-derived exosomes, (2) role of exosomes in classically activating M1-like macrophages, oral squamous cell carcinoma-derived exosomes, breast cancer-derived exosomes, Pancreatic-cancer derived modified exosomes, and colorectal cancer-derived exosomes, and (3) exosomes and antibody-dependent cellular cytotoxicity (ADCC). Read More

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The PI3K pathway impacts stem gene expression in a set of glioblastoma cell lines.

J Cancer Res Clin Oncol 2020 Mar 6;146(3):593-604. Epub 2020 Feb 6.

Department of Biology, University of Texas-Rio Grande Valley, 1201 W. University Dr., Room: ESCNE 4.633, Edinburg, TX, 78539, USA.

Background: The PI3K pathway controls diverse cellular processes including growth, survival, metabolism, and apoptosis. Nuclear FOXO factors were observed in cancers that harbor constitutively active PI3K pathway output and stem signatures. FOXO1 and FOXO3 were previously published to induce stem genes such as OCT4 in embryonic stem cells. Read More

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Dissecting the role of crosstalk between glioblastoma subpopulations in tumor cell spreading.

Oncogenesis 2020 Feb 5;9(2):11. Epub 2020 Feb 5.

Department for Bio-Medical Research, Faculty of Dental Medicine, Hebrew University of Jerusalem, Jerusalem, 91120, Israel.

Glioblastoma (GBM) is a highly infiltrative brain cancer, which is thus difficult to operate. GBM cells frequently harbor Epidermal Growth Factor Receptor amplification (EGFRwt) and/or activating mutation (EGFRvIII), generating at least two different cellular subpopulations within the tumor. We examined the relationship between the diffusive architectures of GBM tumors and the paracrine interactions between those subpopulations. Read More

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February 2020

Adult Human Glioblastomas Harbor Radial Glia-like Cells.

Stem Cell Reports 2020 02 30;14(2):338-350. Epub 2020 Jan 30.

Department of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address:

Radial glia (RG) cells are the first neural stem cells to appear during embryonic development. Adult human glioblastomas harbor a subpopulation of RG-like cells with typical RG morphology and markers. The cells exhibit the classic and unique mitotic behavior of normal RG in a cell-autonomous manner. Read More

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February 2020

Longitudinal assessment of tumor development using cancer avatars derived from genetically engineered pluripotent stem cells.

Nat Commun 2020 Jan 28;11(1):550. Epub 2020 Jan 28.

Ludwig Cancer Research San Diego Branch, 9500 Gilman Dr., CMM-East Room 3055, La Jolla, CA, 92093, USA.

Many cellular models aimed at elucidating cancer biology do not recapitulate pathobiology including tumor heterogeneity, an inherent feature of cancer that underlies treatment resistance. Here we introduce a cancer modeling paradigm using genetically engineered human pluripotent stem cells (hiPSCs) that captures authentic cancer pathobiology. Orthotopic engraftment of the neural progenitor cells derived from hiPSCs that have been genome-edited to contain tumor-associated genetic driver mutations revealed by The Cancer Genome Atlas project for glioblastoma (GBM) results in formation of high-grade gliomas. Read More

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January 2020

Prognostic and radiographic correlates of a prospectively collected molecularly profiled cohort of IDH1/2-wildtype astrocytomas.

Brain Pathol 2020 05 12;30(3):653-660. Epub 2020 Feb 12.

Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065.

Background: In the molecular era, the relevance of tumor grade for prognostication of IDH1/2-wildtype (WT) gliomas has been debated. It has been suggested that histologic grade II and III astrocytomas with molecular features of glioblastoma, IDH1/2-WT have a similar prognosis to glioblastoma and should be considered for the same clinical trials.

Methods: We integrated prospective clinical sequencing from 564 patients with IDH1/2-WT gliomas (26 grade II, 71 grade III and 467 grade IV) with clinical and radiographic data to assess associations between molecular features, grade and outcome. Read More

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Germline cancer predisposition variants and pediatric glioma: a population-based study in California.

Neuro Oncol 2020 06;22(6):864-874

Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California.

Background: Pediatric astrocytoma constitutes a majority of malignant pediatric brain tumors. Previous studies that investigated pediatric cancer predisposition have primarily been conducted in tertiary referral centers and focused on cancer predisposition genes. In this study, we investigated the contribution of rare germline variants to risk of malignant pediatric astrocytoma on a population level. Read More

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