scholarly journals DIPG-60. PILOT STUDY OF CIRCULATING TUMOR CELLS IN PEDIATRIC HIGH GRADE BRAIN TUMORS

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii299-iii299
Author(s):  
Wafik Zaky ◽  
Long Dao ◽  
Dristhi Ragoonanan ◽  
Izhar Bath ◽  
Sofia Yi ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Brain Tumors ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Pediatric Brain Tumor ◽  
Pediatric Brain Tumors ◽  
Disease Assessment ◽  
Liquid Biopsies ◽  
Capture Method ◽  
Pediatric Brain

Abstract BACKGROUND Despite its increasing use, circulating tumor cells (CTCs) have not been studied in pediatric brain tumors. METHODS Cell surface vimentin (CSV) is a marker for CTC detection. We developed an automated CSV-based CTC capture method for pediatric brain tumor using the Abnova Cytoquest platform. PBMCs isolated from blood samples from 52 brain tumor patients were processed to isolate CSV+ CTCs. Captured cells were then stained for CSV and CD45 and scanned to determine the number of CTCs. DIPG samples were additionally examined for H3K27M expression on CSV+ cells. Long term cancer survivors were used as a control cohort. RESULTS 86.4% of all the samples exhibited between 1–13 CSV+ CTCs, with a median of 2 CSV+ CTCs per sample. Using a value of ≥ 1 CTC as a positive result, the sensitivity and specificity of this test was 83.05% and 60.0% respectively. 19 DIPG samples were analyzed and 70% (13 samples) were positive for 1–5 CTCs. Five of these 7 positive CSV+ CTCs DIPG samples were also positive for H3K27M mutations by immunohistochemistry (71%). Mean survival in days for the CTC positive and negative DIPG samples were 114 and 211 days, respectively (p= 0.13). CONCLUSION This is the first study of CTCs in pediatric CNS tumors using an automated approach. Patients with brain tumors can exhibit CSV+ CTCs within peripheral blood. The use of specific molecular markers such as H3K27M can improve the diagnostic capability of liquid biopsies and may enable future disease assessment for personalized therapy.

scholarly journals A pediatric brain tumor atlas of genes deregulated by somatic genomic rearrangement

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yiqun Zhang ◽  
Fengju Chen ◽  
Lawrence A. Donehower ◽  
Michael E. Scheurer ◽  
Chad J. Creighton
Keyword(s):  
Brain Tumor ◽  
Brain Tumors ◽  
Tyrosine Kinases ◽  
Pediatric Brain Tumor ◽  
Pediatric Brain Tumors ◽  
Altered Expression ◽  
Critical Pathways ◽  
Cis Regulation ◽  
Or Gene ◽  
Pediatric Brain

AbstractThe global impact of somatic structural variants (SSVs) on gene expression in pediatric brain tumors has not been thoroughly characterised. Here, using whole-genome and RNA sequencing from 854 tumors of more than 30 different types from the Children’s Brain Tumor Tissue Consortium, we report the altered expression of hundreds of genes in association with the presence of nearby SSV breakpoints. SSV-mediated expression changes involve gene fusions, altered cis-regulation, or gene disruption. SSVs considerably extend the numbers of patients with tumors somatically altered for critical pathways, including receptor tyrosine kinases (KRAS, MET, EGFR, NF1), Rb pathway (CDK4), TERT, MYC family (MYC, MYCN, MYB), and HIPPO (NF2). Compared to initial tumors, progressive or recurrent tumors involve a distinct set of SSV-gene associations. High overall SSV burden associates with TP53 mutations, histone H3.3 gene H3F3C mutations, and the transcription of DNA damage response genes. Compared to adult cancers, pediatric brain tumors would involve a different set of genes with SSV-altered cis-regulation. Our comprehensive and pan-histology genomic analyses reveal SSVs to play a major role in shaping the transcriptome of pediatric brain tumors.

scholarly journals SL1 GENETICS OF PEDIATRIC BRAIN TUMORS: RECENT ADVANCES AND FUTURE PERSPECTIVES

2019 ◽  
Vol 1 (Supplement_2) ◽  
pp. ii1-ii1
Author(s):  
David T W Jones
Keyword(s):  
Brain Tumor ◽  
Brain Tumors ◽  
Somatic Hypermutation ◽  
Tumor Biology ◽  
Pediatric Brain Tumor ◽  
Pediatric Brain Tumors ◽  
Braf V600e ◽  
Enhancer Element ◽  
Frequent Mutations ◽  
Pediatric Brain

Abstract The last decade has seen a true revolution in our understanding of the oncogenic mechanisms underlying human tumors, brought about by transformative advances in the technologies available to interrogate the (epi)genetic composition of cancer cells. The dynamic pediatric neuro-oncology community has proven to be very agile in adapting to these changes, and has arguably been at the forefront of some of the most exciting new discoveries in tumor biology in recent years. For example, high-throughput genomic sequencing has revealed highly frequent mutations in histone genes in pediatric glioblastoma; highlighted an ever-expanding role for oncogenic gene fusions in multiple pediatric brain tumor types, and also shed light on novel phenotypic patterns such as chromothripsis (dramatic chromosomal shattering) and somatic hypermutation - the latter being a possible marker for response to novel immunotherapeutic approaches. Epigenetic profiling has also identified a role for ‘enhancer hijacking’ (whereby genomic rearrangement brings an active enhancer element in close proximity to a proto-oncogene) in multiple pediatric brain tumors, and is even pointing towards a fundamentally new way in which tumors may be molecularly classified. In coming years, the major challenge will be to harness the power of these discoveries to more accurately diagnose patients and to identify potential therapeutic targets in a more personalized way, so that these major biological advances can also be translated into substantial clinical benefit. Examples such as the dramatic responses observed in childhood brain tumor sufferers to BRAF V600E and NTRK inhibitors demonstrate the promise that such an approach can hold, but it will require a fundamental shift in the way that clinical trials are planned and conducted in order to optimize patient care. This talk will highlight some of the most striking developments in the field, and look at the challenges that remain before these can lead to improved patient outcomes.

scholarly journals Exploratory Evaluation of MR Permeability with 18F-FDG PET Mapping in Pediatric Brain Tumors: A Report from the Pediatric Brain Tumor Consortium

2013 ◽  
Vol 54 (8) ◽  
pp. 1237-1243 ◽  
Author(s):  
K. A. Zukotynski ◽  
F. H. Fahey ◽  
S. Vajapeyam ◽  
S. S. Ng ◽  
M. Kocak ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Brain Tumors ◽  
Fdg Pet ◽  
Pediatric Brain Tumor ◽  
Pediatric Brain Tumors ◽  
18F Fdg ◽  
Pediatric Brain

scholarly journals Circular RNA expression profiles in pediatric ependymomas

2020 ◽  
Author(s):  
Ulvi Ahmadov ◽  
Meile M. Bendikas ◽  
Karoline K. Ebbesen ◽  
Astrid M. Sehested ◽  
Jorgen Kjems ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Brain Tumors ◽  
Pilocytic Astrocytoma ◽  
Expression Profiles ◽  
Pediatric Brain Tumor ◽  
Pediatric Brain Tumors ◽  
Disease Stage ◽  
Tumor Subtypes ◽  
Pediatric Brain ◽  
Control Samples

Pediatric brain tumors frequently develop in the cerebellum, where ependymoma, medulloblastoma and pilocytic astrocytoma are the most prevalent subtypes. These tumors are currently treated using non-specific therapies, in part because few somatically mutated driver genes are present, and the underlying pathobiology is poorly described. Circular RNAs (circRNAs) have recently emerged as a large class of primarily non-coding RNAs with important roles in tumorigenesis, but so far they have not been described in pediatric brain tumors. To advance our understanding of these tumors, we performed high-throughput sequencing of ribosomal RNA-depleted total RNA from 10 primary ependymoma and 3 control samples. CircRNA expression patterns were determined using two independent bioinformatics algorithms, and correlated to disease stage, outcome, age, and gender. We found a profound global downregulation of circRNAs in ependymoma relative to control samples. Many differentially expressed circRNAs were discovered and circSMARCA5 and circ-FBXW7, which are described as tumor suppressors in glioma and glioblastomas in adults, were among the most downregulated. Moreover, patients with a dismal outcome clustered separately from patients with a good prognosis in unsupervised hierarchical cluster analyses. Next, we performed NanoString nCounter experiments using a custom-designed panel including 66 selected circRNA targets and analyzed formalin-fixed paraffin-embedded (FFPE) samples from a larger cohort of ependymoma patients as well as patients diagnosed with medulloblastoma or pilocytic astrocytoma. These experiments were used to validate our findings and, in addition, indicated that circRNA expression profiles are different among distinct pediatric brain tumor subtypes. In particular, circRMST and a circRNA derived from the LRBA gene were specifically upregulated in ependymomas. In conclusion, circRNAs have profoundly different expression profiles in ependymomas relative to controls and other pediatric brain tumor subtypes.

scholarly journals Deep Learning-Based Studies on Pediatric Brain Tumors Imaging: Narrative Review of Techniques and Challenges

2021 ◽  
Vol 11 (6) ◽  
pp. 716
Author(s):  
Hala Shaari ◽  
Jasmin Kevrić ◽  
Samed Jukić ◽  
Larisa Bešić ◽  
Dejan Jokić ◽  
...  
Keyword(s):  
Deep Learning ◽  
Brain Tumor ◽  
Brain Tumors ◽  
Tumor Imaging ◽  
Pediatric Brain Tumor ◽  
Pediatric Brain Tumors ◽  
Research Issues ◽  
Functional Changes ◽  
Imaging Results ◽  
Pediatric Brain

Brain tumors diagnosis in children is a scientific concern due to rapid anatomical, metabolic, and functional changes arising in the brain and non-specific or conflicting imaging results. Pediatric brain tumors diagnosis is typically centralized in clinical practice on the basis of diagnostic clues such as, child age, tumor location and incidence, clinical history, and imaging (Magnetic resonance imaging MRI / computed tomography CT) findings. The implementation of deep learning has rapidly propagated in almost every field in recent years, particularly in the medical images’ evaluation. This review would only address critical deep learning issues specific to pediatric brain tumor imaging research in view of the vast spectrum of other applications of deep learning. The purpose of this review paper is to include a detailed summary by first providing a succinct guide to the types of pediatric brain tumors and pediatric brain tumor imaging techniques. Then, we will present the research carried out by summarizing the scientific contributions to the field of pediatric brain tumor imaging processing and analysis. Finally, to establish open research issues and guidance for potential study in this emerging area, the medical and technical limitations of the deep learning-based approach were included.

scholarly journals Peripheral circulation miRNA expression of pediatric brain tumors and its relation to tumor miRNA expression levels

2020 ◽  
Vol 26 (2) ◽  
pp. 136-144 ◽  
Author(s):  
Markus Bookland ◽  
Eileen Gillan ◽  
Xianyuan Song ◽  
Antonina Kolmakova
Keyword(s):  
Brain Tumor ◽  
Brain Tumors ◽  
Mirna Expression ◽  
Tumor Tissue ◽  
Pediatric Brain Tumor ◽  
Pediatric Brain Tumors ◽  
Tumor Patients ◽  
Tumor Patient ◽  
Serum Mirna ◽  
Pediatric Brain

OBJECTIVEMicro RNAs (miRNAs) in peripheral biofluids (e.g., blood, saliva, urine) have been investigated as potential sources of diagnostic and prognostic information for a variety of tumor types, including pediatric brain tumors. While significant predictive associations have been identified between unique serum miRNA concentrations and some pediatric brain tumors, it is unclear whether serum miRNA abnormalities in pediatric brain tumor patients are representative of miRNA alterations in the tumor tissue compartment or whether they represent host tissue reactions to the presence of a brain tumor. The authors sought to identify whether serum miRNA changes in pediatric brain tumor patient sera could be explained by miRNA alterations within their tumors.METHODSMatched serum and tissue samples were taken from a cohort of pediatric brain tumor patients (juvenile pilocytic astrocytoma [JPA] = 3, medulloblastoma = 4, ependymoma = 3), and unmatched control samples (n = 5) were acquired from control pediatric patients without oncological diagnoses. Extracted RNAs were tested within an array of 84 miRNAs previously noted to be relevant in a variety of brain tumors.RESULTSmiR-26a-5p correlated strongly in JPA patients within both the serum and tumor tissue samples (R2 = 0.951, p = 0.046), and serum levels were highly predictive of JPA (area under the curve = 0.751, p = 0.027). No other miRNAs that were significantly correlated between biological compartments were significantly associated with brain tumor type. In total, 15 of 84 tested miRNAs in JPA patients, 14 of 84 tested miRNAs in ependymoma patients, and 4 of 84 tested miRNAs in medulloblastoma patients were significantly, positively correlated between serum and tumor tissue compartments (R2 > 0.950, p < 0.05).CONCLUSIONSThe majority of miRNA changes in pediatric brain tumor patient sera that are significantly associated with the presence of a brain tumor do not correlate with brain tumor miRNA expression levels. This suggests that peripheral miRNA changes within pediatric brain tumor patients likely derive from tissues other than the tumors themselves.

scholarly journals TBIO-16. AUTOMATED CELL ENRICHMENT AND DIGITAL CELL SORTING USING DIELECTROPHORETIC ARRAYS FOR ISOLATION OF CIRCULATING TUMOR CELLS IN PEDIATRIC BRAIN TUMOR PATIENTS

2018 ◽  
Vol 20 (suppl_2) ◽  
pp. i183-i183
Author(s):  
Katherine Barnett ◽  
Kaicen Zhu ◽  
Guomiao Shen ◽  
Jonathan Serrano ◽  
David Harter ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Cell Sorting ◽  
Pediatric Brain Tumor ◽  
Tumor Patients ◽  
Cell Enrichment ◽  
Pediatric Brain

scholarly journals Liquid biopsies for the diagnosis and surveillance of primary pediatric central nervous system tumors: a review for practicing neurosurgeons

2020 ◽  
Vol 48 (1) ◽  
pp. E8 ◽  
Author(s):  
Michael T. Bounajem ◽  
Michael Karsy ◽  
Randy L. Jensen
Keyword(s):  
Brain Tumor ◽  
Brain Tumors ◽  
Pediatric Brain Tumors ◽  
Response To Treatment ◽  
Prognostic Indicators ◽  
Monitoring Methods ◽  
Liquid Biopsies ◽  
Mesh Terms ◽  
Pediatric Brain ◽  
Tumor Dna

OBJECTIVEPrimary brain tumors are the most common cause of cancer-related deaths in children and pose difficult questions for the treating physician regarding issues such as the risk/benefit of performing a biopsy, the accuracy of monitoring methods, and the availability of prognostic indicators. It has been recently shown that tumor-specific DNA and proteins can be successfully isolated in liquid biopsies, and it may be possible to exploit this potential as a particularly useful tool for the clinician in addressing these issues.METHODSA review of the current literature was conducted by searching PubMed and Scopus. MeSH terms for the search included “liquid biopsy,” “brain,” “tumor,” and “pediatrics” in all fields. Articles were reviewed to identify the type of brain tumor involved, the method of tumor DNA/protein analysis, and the potential clinical utility. All articles involving primary studies of pediatric brain tumors were included, but reviews were excluded.RESULTSThe successful isolation of circulating tumor DNA (ctDNA), extracellular vesicles, and tumor-specific proteins from liquid biopsies has been consistently demonstrated. This most commonly occurs through CSF analysis, but it has also been successfully demonstrated using plasma and urine samples. Tumor-related gene mutations and alterations in protein expression are identifiable and, in some cases, have been correlated to specific neoplasms. The quantity of ctDNA isolated also appears to have a direct relationship with tumor progression and response to treatment.CONCLUSIONSThe use of liquid biopsies for the diagnosis and monitoring of primary pediatric brain tumors is a foreseeable possibility, as the requisite developmental steps have largely been demonstrated. Increasingly advanced molecular methods are being developed to improve the identification of tumor subtypes and tumor grades, and they may offer a method for monitoring treatment response. These minimally invasive markers will likely be used in the clinical treatment of pediatric brain tumors in the future.

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