scholarly journals OMIC-13. THE ROLE OF COPY NUMBER ALTERATIONS IN PREDICTING SURVIVAL AND INFLUENCING TREATMENT OF CHILDHOOD BRAIN TUMORS

2021 ◽  
Vol 23 (Supplement_1) ◽  
pp. i40-i40
Author(s):  
Sharon Freshour ◽  
Bryan Fisk ◽  
Christopher Miller ◽  
Obi Griffith ◽  
Malachi Griffith ◽  
...  

Abstract Brain and central nervous system tumors are the most common form of solid tumor cancers and the second most common cancer overall among children. While many advances have been made in understanding the genomics of childhood brain tumors in recent years, the role of copy number alterations (CNAs) has not been fully characterized. Although the genomes of childhood brain tumor patients are generally considered to be relatively stable diploid genomes, analysis of a subset of pretreatment diagnostic samples from a cohort of 84 deceased patients from Washington University revealed widespread alterations, suggesting CNAs may play a larger role in the progression and prognosis of childhood brain tumors than originally thought. Follow up analysis of the entire cohort, containing a variety of tumor types that had low-pass whole genome sequencing performed, similarly showed evidence of CNAs across samples. 75 out 84 patients showed the presence of CNAs with an average of 16% of the genome being altered per sample and a median of 7%. Preliminary results examining correlations between the percentage of the genome that was copy number altered and event free survival or overall survival indicated that CNA percentage may have some prognostic value. For example, ependymoma samples showed positive correlation between alteration percentage and overall survival, while glioblastoma samples showed negative correlation. To explore copy number alteration in a larger cohort and increase statistical power, similar analyses are being performed using an additional 950 samples from the Pediatric Brain Tumor Atlas curated by The Children’s Brain Tumor Network (CBTN) to determine if CNVs and CNV percentage or specific alterations can serve as prognostic markers and whether the biology of this genomic instability could inform therapeutic strategy.

2021 ◽  
Vol 22 (5) ◽  
pp. 2250
Author(s):  
Evita Athanasiou ◽  
Antonios N. Gargalionis ◽  
Fotini Boufidou ◽  
Athanassios Tsakris

The role of certain viruses in malignant brain tumor development remains controversial. Experimental data demonstrate that human herpesviruses (HHVs), particularly cytomegalovirus (CMV), Epstein–Barr virus (EBV) and human herpes virus 6 (HHV-6), are implicated in brain tumor pathology, although their direct role has not yet been proven. CMV is present in most gliomas and medulloblastomas and is known to facilitate oncomodulation and/or immunomodulation, thus promoting cancer cell proliferation, invasion, apoptosis, angiogenesis, and immunosuppression. EBV and HHV-6 have also been detected in brain tumors and high-grade gliomas, showing high rates of expression and an inflammatory potential. On the other hand, due to the neurotropic nature of HHVs, novel studies have highlighted the engagement of such viruses in the development of new immunotherapeutic approaches in the context of oncolytic viral treatment and vaccine-based strategies against brain tumors. This review provides a comprehensive evaluation of recent scientific data concerning the emerging dual role of HHVs in malignant brain pathology, either as potential causative agents or as immunotherapeutic tools in the fight against these devastating diseases.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yiqun Zhang ◽  
Fengju Chen ◽  
Lawrence A. Donehower ◽  
Michael E. Scheurer ◽  
Chad J. Creighton

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.


2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii299-iii299
Author(s):  
Wafik Zaky ◽  
Long Dao ◽  
Dristhi Ragoonanan ◽  
Izhar Bath ◽  
Sofia Yi ◽  
...  

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.


1998 ◽  
Vol 106 ◽  
pp. 887 ◽  
Author(s):  
Susan Preston-Martin ◽  
Janice M. Pogoda ◽  
Beth A. Mueller ◽  
Flora Lubin ◽  
Baruch Modan ◽  
...  

2021 ◽  
Vol 36 (6) ◽  
pp. 1225-1225
Author(s):  
Viannae Carmona ◽  
Dianne Kong ◽  
Ashley M Whitaker

Abstract Objective As the field of neuropsychology strives to provide equitable care among diverse and disadvantaged populations, disparities in treatment and long-term outcomes continue to disproportionately impact individuals of lower socioeconomic status (SES). Motor deficits are common following pediatric brain tumor (PBT) diagnoses. However, while the relationship between SES and cognitive outcomes in this population is well documented, the role of SES in predicting more basic motor outcomes is not yet understood. This retrospective cross-sectional study was designed to determine the impact of SES on fine motor and graphomotor outcomes in PBT patients to ensure appropriate interventions and accommodations for those at higher risk. Method 225 patients with PBT (52.9% male; $ \overset{-}{\textrm{x}} $ age = 12 yrs; SD = 5.3 yrs) underwent neuropsychological evaluation, including assessment of graphomotor speed/coordination, visual-motor integration, and fine motor dexterity. Estimated median household income was used as a proxy for SES ($ \overset{-}{\textrm{x}} $=$71,543; SD = $23,480). Linear regression analyses were used to explore the role of SES in predicting motor outcomes. Results Lower SES predicted poorer graphomotor speed, F(1,96) = 5.205, p = 0.013, graphomotor coordination, F(1,60) = 3.890, p = 0.027, visual-motor integration, F(1,88) = 8.116, p = 0.003, and fine motor dexterity, F(1,166) = 3.755, p = 0.027. All analyses were significant even after implementing false discovery rates. Conclusions Consistent with lower SES predicting poorer cognitive late effects, SES also plays a role in motor-related outcomes of PBT. Unfortunately, lower SES is also associated with barriers in accessing formal evaluations and services required to mitigate such deficits. Therefore, patients with lower SES should be considered higher risk and receive interventions and accommodations even in the absence of formal assessment to prevent delays in care.


Author(s):  
Chikezie Eseonu ◽  
Jordina Rincon-Torroella ◽  
Alfredo Quiñones-Hinojosa

Brain tumor cases make up a significant part of the neurosurgery Oral Board Exam. A multitude of brain tumors exist and can be intraaxial or extraaxial. When considering a differential diagnosis for a brain lesion, infection, hematomas, infarctions, thrombosed aneurysms, inflammation, and demyelinating disease must be considered in addition to tumors. Common adult brain tumors consist of gliomas, meningiomas, metastases, and pituitary tumors. Management of brain tumors consists of understanding preoperative care, indications for surgery, surgical approaches, interpretation of preoperative and postoperative imaging, intraoperative and postoperative complications, and the role of adjuvant therapy, including chemotherapy and radiotherapy. Reviewing these essential points for the most common brain tumor cases and mastering the current treatment recommendations for common tumors will also be helpful for the boards.


Author(s):  
Donald Y. Ye ◽  
Thana Theofanis ◽  
Tomas Garzon-Muvdi ◽  
James J. Evans

Intracranial tumors reflect a broad range of benign and malignant processes that are often managed by neurosurgeons and medical oncologists. Patients presenting with new brain tumors will undergo biopsies or resection for tissue diagnosis and resolution of neurological symptoms. These patients have significant perioperative risk factors that must be addressed to ensure the best possible outcomes. Hospitalists play a pivotal role in identifying these risk factors and offering management strategies prior to the development of an operative plan. This chapter provides insight into the range of preoperative considerations and postoperative complications that a hospitalist may face when managing brain tumor patients.


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