scholarly journals RARE-36. DYSEMBRYOPLASTIC NEUROEPITHELIAL TUMORS: A REVIEW OF CLINICAL AND MOLECULAR CHARACTERISTICS, AND OUTCOME IN A PEDIATRIC POPULATION AT A SINGLE CENTER

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii450-iii450
Author(s):  
Valerie Cruz Flores ◽  
Thomas Geller ◽  
Ignacio Gonzalez Gomez ◽  
Luis Rodriguez ◽  
Javier Quintana ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Pediatric Population ◽  
Molecular Genetic ◽  
Intractable Epilepsy ◽  
Retrospective Chart Review ◽  
Braf V600e ◽  
Molecular Characteristics ◽  
Dysembryoplastic Neuroepithelial Tumor ◽  
Free Standing ◽  
Presenting Symptoms

Abstract BACKGROUND Neuronal and mixed neuro-glial tumors of the central nervous system (CNS) are relatively rare. Dysembryoplastic neuroepithelial tumor (DNET) is a benign, rare, slow-growing tumor, but in many cases is associated with intractable epilepsy. OBJECTIVE To report the experience with DNET at a single free-standing children’s institution. METHODS A retrospective chart review of 24 patients with confirmed DNET between 2001 and 2019 was performed. Data was collected on clinical characteristics, tumor location, surgical management, histopathological and molecular findings, and outcomes. RESULTS Mean age at diagnosis was 10 years (range 2 to 19 years), with female predominance (54.2%). Most common presenting symptoms were seizures (79.2%) and headaches (12.5%). Location of the tumor was temporal (29.2%), frontal (25.0%), parietal (16.7%), cerebellar (12.5%) and occipital (4.2%). A gross total resection was achieved in half the cases. Recurrence occurred in 4 patients (16.7%), all of whom had subtotal resections. The average follow up since diagnosis was 4.6 years (range 0.3 to 14 years). Nineteen patients presented with seizures, of which 63.2% were seizure free after surgery. The samples with molecular genetic testing (microarrays or FISH), were all normal except one patient positive for BRAF V600E mutation. CONCLUSIONS This is the first and largest review of pediatric DNETs in the last 10 years. Despite majority of patients having a favorable outcome after surgery, a subset of patients remains symptomatic. As molecular mechanisms in DNET remain unknown, future aim is to describe the molecular characteristics of our DNET population, and correlate with outcomes.

scholarly journals Clinician's modern approaches to molecular genetic diagnosis of glioblastomas

2021 ◽  
Vol 67 (1) ◽  
pp. 13-19
Author(s):  
Turna Ashkhatcava ◽  
Marina Tatarinova ◽  
Lali Kogoniya ◽  
David Naskhletashvili ◽  
Vadim Zhukov
Keyword(s):  
Braf Mutation ◽  
Molecular Mechanisms ◽  
Molecular Genetic ◽  
Genetic Diagnosis ◽  
Braf V600e ◽  
Poor Prognostic Factor ◽  
Molecular Genetic Diagnosis ◽  
The Brain ◽  
Tert Mutation ◽  
Primary Glioblastomas

The article is devoted to the issue of molecular genetic diagnosis of cerebral glioblastomas. Despite significant advances in neurooncology, little progress has been made in prolonging the life of patients with cerebral glioblastoma, and a significant part of the effectiveness of treatment depends on the recognition of two prognostic biomarkers: mutations of the isocitrate dehydrogenase (IDH) promoter and  the methylation of the O6-methylguanine methyl transferase (MGMT) promoter. The article summarizes the data of world and domestic clinical studies, allowing to supplement the histological characteristics of primary glioblastomas with genetic markers: the presence of the TERT mutation, EFGR amplification, loss of PTEN function, LOH 10q, and the presence of the BRAF mutation. It should be noted that the amplification of EGFR, causing resistance to apoptotic stimuli and alkylating chemotherapy with Temozolomide, attracts much attention as a therapeutic target. The frequency of occurrence of the TERT mutation is 90% of all tumors of various genesis, most often the TERT mutation is found in oligodendroglioma or primary glioblastoma. Loss of heterozygosity in the region of localization of the PTEN gene is observed in many types of sporadic tumors, including more than 40% of glioblastomas. Mutations in this gene are found in tumors of the brain, endometrium, prostate, kidney, and mammary gland. The presence of a PTEN mutation is a poor prognostic factor. LOH 22q is much more common in secondary glioblastomas (82%) than in primary glioblastomas (41%). Among brain tumors, the BRAF mutation is most common with pleomorphic xanastrocytoma (60-70%).The BRAF V600E mutation was found in epithelioid glioblastoma, which is a rare and aggressive type of glioblastoma, characterized by an unfavorable prognosis (about 6 months) and frequent leptomeningeal spread. Thus, knowledge of the molecular mechanisms of carcinogenesis will enable a personalized approach to treatment with glioblastomas of the brain.

scholarly journals Low-grade gliomas with the V600E mutation in the BRAF gene in children: clinical features and treatment options

2020 ◽  
Vol 19 (4) ◽  
pp. 58-65
Author(s):  
L. I. Papusha ◽  
E. F. Valiakhmetova ◽  
A. E. Druy ◽  
L. A. Yasko ◽  
K. A. Voronin ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Treatment Options ◽  
Molecular Genetic ◽  
Braf Inhibitor ◽  
Complete Response ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Molecular Characteristics ◽  
Low Grade ◽  
Low Grade Gliomas

The main pathogenetic mechanism of the development of pediatric low grade gliomas (pLGGs) is genetic aberrations in BRAF gene. This study is supported by the Independent Ethics Committee and approved by the Academic Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology. We analyzed the clinical and molecular characteristics of 69 patients with LGGs. Molecular genetic testing for BRAF V600E mutation was performed by allele-specific real-time PCR and Sanger sequencing. BRAF V600E mutation was detected in 15 (21.7%) patients with LGG. The majority of BRAF-mutated cases of LGGs had the midline location: OPG – 7, subcortical ganglia – 1, brainstem – 2. The 2-year PFS was much worse in patients with BRAF V600E compared to patients without this mutation – 30% and 66.2%, respectively. The median time to progression for patients with BRAF V600E mutation was 9.5 months compared to 3.1 years for patients without indicated substitution. 5 patients with BRAF V600E-mutated LGGs who experienced progression after the conventional treatment, received targeted therapy (BRAF-inhibitor-3, BRAF + MEK inhibitors – 2) with good response (complete response – 2, partial response – 3). BRAF V600E mutation contributes to poor outcome in patients with LGGs Targeted therapy could be effective in this cohort of patients.

Molecular Basis and Clinical Aspects of Hereditary Megakaryocyte and Platelet Membrane Glycoprotein Disorders

1996 ◽  
Vol 16 (02) ◽  
pp. 114-138 ◽  
Author(s):  
R. E. Scharf
Keyword(s):  
Genetic Basis ◽  
Molecular Mechanisms ◽  
Molecular Genetic ◽  
Platelet Membrane ◽  
Clinical Aspects ◽  
Membrane Glycoprotein ◽  
Membrane Glycoproteins ◽  
Membrane Expression ◽  
Receptor Complexes ◽  
Platelet Membrane Glycoprotein

SummarySpecific membrane glycoproteins (GP) expressed by the megakaryocyte-platelet system, including GPIa-lla, GPIb-V-IX, GPIIb-llla, and GPIV are involved in mediat-ing platelet adhesion to the subendothelial matrix. Among these glycoproteins, GPIIb-llla plays a pivotal role since platelet aggregation is exclusively mediated by this receptor and its interaction with soluble macromolecular proteins. Inherited defects of the GPIIb-llla or GPIb-V-IX receptor complexes are associated with bleeding disorders, known as Glanzmann's thrombasthenia, Bernard-Soulier syndrome, or platelet-type von Willebrand's disease, respectively. Using immuno-chemical and molecular biology techniques, rapid advances in our understanding of the molecular genetic basis of these disorders have been made during the last few years. Moreover, analyses of patients with congenital platelet membrane glycoprotein abnormalities have provided valuable insights into molecular mechanisms that are required for structural and functional integrity, normal biosynthesis of the glycoprotein complexes and coordinated membrane expression of their constituents. The present article reviews the current state of knowledge of the major membrane glycoproteins in health and disease. The spectrum of clinical bleeding manifestations and established diagnostic criteria for each of these dis-orders are summarized. In particular, the variety of molecular defects that have been identified so far and their genetic basis will be discussed.

scholarly journals A national study of choanal atresia in tertiary care centers in Canada – part I: clinical presentation

2021 ◽  
Vol 50 (1) ◽  
Author(s):  
Josee Paradis ◽  
Agnieszka Dzioba ◽  
Hamdy El-Hakim ◽  
Paul Hong ◽  
Frederick K. Kozak ◽  
...  
Keyword(s):  
Respiratory Distress ◽  
Clinical Presentation ◽  
Tertiary Care ◽  
Choanal Atresia ◽  
Case Series ◽  
Retrospective Chart Review ◽  
National Study ◽  
Feeding Difficulties ◽  
Presenting Symptoms ◽  
Tertiary Care Centers

Abstract Background To evaluate the clinical presentation of choanal atresia (CA) in tertiary centers across Canada. Methods Multi-centre case series involving six tertiary care pediatric hospitals across Canada. Retrospective chart review of patients born between 1980 and 2010 diagnosed with CA at a participating center. Results The health charts of 215 patients (59.6% female) with CA were reviewed and included in this study. The mean age of patients at time of CA presentation was 0.4 months (range 0.1 to 7.2 months) for bilateral CA and 37.8 months (range 0.1 to 164.1 months) for unilateral cases. The most common presenting symptoms for bilateral CA in decreasing order were respiratory distress (96.4%), feeding difficulties (68.2%), and rhinorrhea (65.5%), and for unilateral cases in decreasing order were rhinorrhea (92.0%), feeding difficulties (24.7%), and respiratory distress (18.0%). For the majority of patients (73.2%), the obstruction comprised mixed bony and membranous tissue, with only 10.5% presenting with a purely membranous obstruction. Familial history of CA was confirmed in only 3.3% of cases. One half of patients with CA presented with one or more associated anomalies and 30.6% had a syndrome. Conclusions The present investigation is the first national multi-institutional study evaluating the clinical presentation of CA over three decades. The present cohort of CA patients presented with a breadth of co-morbidities with highly variable presentations, with bilateral cases being more severely affected than unilateral cases. Further investigation into hereditary linkages to CA development is warranted. Graphical abstract

scholarly journals Molecular Mechanisms of Drug Resistance in Glioblastoma

2021 ◽  
Vol 22 (12) ◽  
pp. 6385
Author(s):  
Maya A. Dymova ◽  
Elena V. Kuligina ◽  
Vladimir A. Richter
Keyword(s):  
Drug Resistance ◽  
Brain Tumor ◽  
Molecular Mechanisms ◽  
Primary Brain Tumor ◽  
Therapeutic Resistance ◽  
Molecular Characteristics ◽  
Blood Brain ◽  
Conventional Radiation ◽  
The Brain ◽  
Made In

Glioblastoma multiforme (GBM) is the most common and fatal primary brain tumor, is highly resistant to conventional radiation and chemotherapy, and is not amenable to effective surgical resection. The present review summarizes recent advances in our understanding of the molecular mechanisms of therapeutic resistance of GBM to already known drugs, the molecular characteristics of glioblastoma cells, and the barriers in the brain that underlie drug resistance. We also discuss the progress that has been made in the development of new targeted drugs for glioblastoma, as well as advances in drug delivery across the blood–brain barrier (BBB) and blood–brain tumor barrier (BBTB).

Distinctive gene expression profiles of CD34 cells from patients with myelodysplastic syndrome characterized by specific chromosomal abnormalities

Blood ◽  
2004 ◽  
Vol 104 (13) ◽  
pp. 4210-4218 ◽  
Author(s):  
Guibin Chen ◽  
Weihua Zeng ◽  
Akira Miyazato ◽  
Eric Billings ◽  
Jaroslaw P. Maciejewski ◽  
...  
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Small Sample ◽  
Hematopoietic Progenitor Cell ◽  
Molecular Characteristics ◽  
Hematopoietic Progenitor ◽  
Trisomy 8 ◽  
Monosomy 7 ◽  
Cd34 Cells

Abstract Aneuploidy, especially monosomy 7 and trisomy 8, is a frequent cytogenetic abnormality in the myelodysplastic syndromes (MDSs). Patients with monosomy 7 and trisomy 8 have distinctly different clinical courses, responses to therapy, and survival probabilities. To determine disease-specific molecular characteristics, we analyzed the gene expression pattern in purified CD34 hematopoietic progenitor cells obtained from MDS patients with monosomy 7 and trisomy 8 using Affymetrix GeneChips. Two methods were employed: standard hybridization and a small-sample RNA amplification protocol for the limited amounts of RNA available from individual cases; results were comparable between these 2 techniques. Microarray data were confirmed by gene amplification and flow cytometry using individual patient samples. Genes related to hematopoietic progenitor cell proliferation and blood cell function were dysregulated in CD34 cells of both monosomy 7 and trisomy 8 MDS. In trisomy 8, up-regulated genes were primarily involved in immune and inflammatory responses, and down-regulated genes have been implicated in apoptosis inhibition. CD34 cells in monosomy 7 showed up-regulation of genes inducing leukemia transformation and tumorigenesis and apoptosis and down-regulation of genes controlling cell growth and differentiation. These results imply distinct molecular mechanisms for monosomy 7 and trisomy 8 MDS and implicate specific pathogenic pathways.

scholarly journals 526. Clinical Presenting Characteristics of Pediatric COVID-19 Infection in a Tertiary Care Children’s Hospital in Detroit

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S330-S330
Author(s):  
Jocelyn Y Ang ◽  
Nirupama Kannikeswaran ◽  
Basim Asmar
Keyword(s):  
Mechanical Ventilation ◽  
Severe Disease ◽  
Tertiary Care ◽  
Retrospective Chart Review ◽  
Signs And Symptoms ◽  
Pediatric Emergency ◽  
Study Cohort ◽  
Mild Disease ◽  
Presenting Symptoms ◽  
Patient Disposition

Abstract Background There is limited data regarding the presenting clinical characteristics of COVID-19 in children. Our objective is to describe the clinical presentations and outcomes of COVID-19 infection early in the pandemic at our institution. Methods We performed a retrospective chart review of children up to 18 years who underwent testing for SARS CoV-2 from March 1st to May 10th 2020 at our pediatric emergency department. We abstracted patient’s demographics, clinical presentation, diagnostic studies and patient disposition. We classified the severity of clinical illness based on published criteria. We excluded patients diagnosed with Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19. Results SARS CoV-2 testing was performed on 481 patients of whom 43 (8.9%) tested positive. Of these, 4 were diagnosed with MIS-C. Data of 39 patients were analyzed. Patients’ demographics, co-morbidities, presenting signs and symptoms and disposition are shown in Table 1. Age range was 47 days – 18 years. Infants representing one third (14/39; 35.9%) of our study cohort. There was equal sex distribution. Asthma or obesity was present in 17 (44%). The most common presenting symptoms included fever, cough, shortness of breath and diarrhea. Chest radiograph showed pneumonia in 12 (30.8%) patients. Two thirds (27/39; 69.2%) were asymptomatic or had mild disease; six patients (15.4%) had severe or critical illness (Figure 1). Nineteen (48%) patients were admitted to the general pediatric service. Eleven (28%) were admitted to the Intensive Care Units (ICU). The characteristics, presenting symptoms and interventions performed in the PICU cohort are shown in Table 2. Half of these patients required mechanical ventilation. There was one death in a 3 month old infant unrelated to SARS CoV-2. Majority of the infants required hospitalization (12/14; 85.7%), including 4 to the PICU (one each for non accidental trauma, ingestion, seizure and pneumonia). Table 1. Patient demographics, signs and symptoms of COVID-19 infection in Children Table 2: PICU patients: Characteristics, Interventions and pharmacotherapy Figure 1: Severity of Ill ness in the study cohort Conclusion Majority (17; 43%) of our children with COVID-19 had a mild disease. Eleven (28%) including 4 infants required critical care; 5 required mechanical ventilation. There was no COVID-19 related mortality. Larger studies are needed to further define the spectrum of COVID- 19 and risk factors associated with severe disease in children. Disclosures All Authors: No reported disclosures

Molecular Alterations in Pediatric Low-Grade Gliomas That Led to Death

2021 ◽  
Author(s):  
Jared T Ahrendsen ◽  
Claire Sinai ◽  
David M Meredith ◽  
Seth W Malinowski ◽  
Tabitha M Cooney ◽  
...  
Keyword(s):  
Braf V600e ◽  
Molecular Characteristics ◽  
Low Grade ◽  
Diffuse Astrocytoma ◽  
Term Survival ◽  
Pten Loss ◽  
Low Grade Gliomas ◽  
Molecular Alterations ◽  
Idh1 R132h ◽  
Poor Outcomes

Abstract Pediatric low-grade gliomas (PLGGs) have excellent long-term survival, but death can occasionally occur. We reviewed all PLGG-related deaths between 1975 and 2019 at our institution: 48 patients were identified; clinical data and histology were reviewed; targeted exome sequencing was performed on available material. The median age at diagnosis was 5.2 years (0.4–23.4 years), at death was 13.0 years (1.9–43.2 years), and the overall survival was 7.2 years (0.0–33.3 years). Tumors were located throughout CNS, but predominantly in the diencephalon. Diagnoses included low-grade glioma, not otherwise specified (n = 25), pilocytic astrocytoma (n = 15), diffuse astrocytoma (n = 3), ganglioglioma (n = 3), and pilomyxoid astrocytoma (n = 2). Recurrence occurred in 42/48 cases, whereas progression occurred in 10. The cause of death was direct tumor involvement in 31/48 cases. Recurrent drivers included KIAA1549-BRAF (n = 13), BRAF(V600E) (n = 3), NF1 mutation (n = 3), EGFR mutation (n = 3), and FGFR1-TACC1 fusion (n = 2). Single cases were identified with IDH1(R132H), FGFR1(K656E), FGFR1 ITD, FGFR3 gain, PDGFRA amplification, and mismatch repair alteration. CDKN2A/B, CDKN2C, and PTEN loss was recurrent. Patients who received only chemotherapy had worse survival compared with patients who received radiation and chemotherapy. This study demonstrates that PLGG that led to death have diverse molecular characteristics. Location and co-occurring molecular alterations with malignant potential can predict poor outcomes.

384 Post-Operative ICU Admission for Elective Craniotomy for Intra-axial Brain Tumor Resection

Neurosurgery ◽  
2017 ◽  
Vol 64 (CN_suppl_1) ◽  
pp. 291-292
Author(s):  
Farhan A Mirza ◽  
Catherine Y Wang ◽  
Thomas Pittman
Keyword(s):  
Brain Tumor ◽  
Pediatric Patients ◽  
Prolonged Mechanical Ventilation ◽  
Pediatric Population ◽  
External Ventricular Drain ◽  
Tumor Resection ◽  
Retrospective Chart Review ◽  
Icu Admission ◽  
Icu Stay ◽  
Brain Tumor Resection

Abstract INTRODUCTION We reviewed our practice at the University of Kentucky in order to assess the safety of admitting adult and pediatric patients to floor beds after craniotomy, exclusively for intra-axial brain tumor resection. METHODS Retrospective chart review of patients, adults and pediatric, who underwent craniotomy by a single surgeon (TP) for intra axial brain tumor resection between January 2012 and December 2015. 413 patient charts were reviewed, 16 were omitted due to incomplete records. RESULTS >421 craniotomies for intra axial brain tumor resection were performed. 397 patients underwent surgery, 35 of whom were <18 years of age.188 females and 209 males. 351 patients (331 adults, 20 pediatric) were admitted to floor beds. In this group, length of operation was <4 hours in 346 patients (99.1%) and >4 hours in only 5 patients (0.9%). 3 patients (0.8%) required transfer to ICU within 24 hours of floor admission. 55 adult patients required ICU stay for various reasons: 9 patients had pre-operative or intra operative EVD placement; 15 patients required prolonged ventilation; 1 patient had to be taken back to the operating room for hemorrhage evacuation; 5 had intraventricular tumors and were planned ICU admissions; 26 patients were admitted pre-operatively to an ICU bed on a non neurosurgical service and were returning to their assigned beds. In the pediatric population, 15 patients required ICU stay: 8 were for EVD management and 7 for prolonged operation or frequent neurological evaluations. In this group, the length of operation was <4 hours in 40 patients(57.1%) and >4 hours in 30 patients (42.9%). CONCLUSION Admitting adult and pediatric patients to floor beds after craniotomy for intra-axial brain tumor resection is safe. There are some conditions that mandate ICU admission: these include prolonged mechanical ventilation and the presence of an external ventricular drain.

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