Germline loss-of-function variant in the E3 ubiquitin ligase TRAF2 in a young adult patient with medulloblastoma: a case report.

We identified a rare heterozygous germline loss-of-function variant in the tumor necrosis factor receptor-associated factor 2 (TRAF2) in a young adult patient diagnosed with medulloblastoma. This variant is located within the TRAF-C domain of the E3 ubiquitin ligase protein and is predicted to diminish the binding affinity of TRAF2 to upstream receptors and associated adaptor proteins. Integrative genomics revealed a biallelic loss of TRAF2 via partial copy-neutral loss-of-heterozygosity of 9q in the medulloblastoma genome.

Permanent cilia loss during cerebellar granule cell neurogenesis involves withdrawal of cilia maintenance and centriole capping.

Brain neurons utilize the primary cilium as a privileged compartment to detect and respond to extracellular ligands such as Sonic hedgehog (SHH). However, cilia in cerebellar granule cell (GC) neurons disassemble during differentiation through ultrastructurally unique intermediates, a process we refer to as cilia deconstruction. In addition, mature neurons do not reciliate despite having docked centrioles.

HIPSD&R-seq enables scalable genomic copy number and transcriptome profiling.

Single-cell DNA sequencing (scDNA-seq) enables decoding somatic cancer variation. Existing methods are hampered by low throughput or cannot be combined with transcriptome sequencing in the same cell. We propose HIPSD&R-seq (HIgh-throughPut Single-cell Dna and Rna-seq), a scalable yet simple and accessible assay to profile low-coverage DNA and RNA in thousands of cells in parallel.

SMURF1 and SMURF2 directly target GLI1 for ubiquitination and proteasome-dependent degradation.

The transcription factor GLI1 is the main and final effector of the Hedgehog signaling pathway, which is involved in embryonic development, cell proliferation and stemness. Whether activated through canonical or non-canonical mechanisms, GLI1 aberrant activity is associated with Hedgehog-dependent cancers, including medulloblastoma, as well as other tumoral contexts. Notwithstanding a growing body of evidence, which have highlighted the potential role of post translational modifications of GLI1, the complex mechanisms modulating GLI1 stability and activity have not been fully elucidated.

Epidemiology and clinical outcomes of childhood central nervous system cancers in a large low-middle income country pediatric oncology center: a report on 5051 kids.

Background: Central nervous system (CNS) tumors are the leading cause of cancer-related deaths in children. While most cases come from low-middle income countries (LMIC) where their prognosis is worse, few epidemiological studies are conducted in these regions.

Methods: We conducted a registry-based cohort study for childhood CNS tumors at Children's Cancer Hospital, Egypt (CCHE) over 15 years.

Detection of human brain cancers using genomic and immune cell characterization of cerebrospinal fluid through CSF-BAM.

Unlabelled: Patients who have radiographically detectable lesions in their brain or other symptoms compatible with brain tumors pose challenges for diagnosis. The only definitive way to diagnose such patients is through brain biopsy, an obviously invasive and dangerous procedure. Here we present a new workflow termed "CSF-BAM" that simultaneously identifies cell or T cell receptor rearrangements, neuploidy, and using PCR-mediated amplification of both strands of the DNA from CSF samples.

A predictive model for cerebellar mutism syndrome based on lesion map in children with medulloblastoma.

Background: This study aimed to establish a voxel-based map to predict the occurrence of cerebellar mutism syndrome (CMS) and investigate the relationship between CMS and motor dysfunction.

Method: This multicenter study cohort included 224 patients diagnosed with medulloblastoma at Beijing Children's Hospital (n = 88) and Beijing Tiantan Hospital (n = 136). The dataset was randomly divided into training (n = 95), test (n = 41), and validation (n = 88) datasets.

Preclinical and Clinical-Scale Magnetic Particle Imaging of Natural Killer Cells: in vitro and ex vivo Demonstration of Cellular Sensitivity, Resolution, and Quantification.

Purpose: Clinical adoption of NK cell immunotherapy is underway for medulloblastoma and osteosarcoma, however there is currently little feedback on cell fate after administration. We propose magnetic particle imaging (MPI) may have applications for the quantitative detection of NK cells.

Procedures: Human-derived NK-92 cells were labeled by co-incubation with iron oxide nanoparticles (VivoTrax™) for 24 h then excess nanoparticles were washed with centrifugation.

OrthologAL: A Shiny application for quality-aware humanization of non-human pre-clinical high-dimensional gene expression data.

Single-cell and spatial transcriptomics provide unprecedented insight into the inner workings of disease. Pharmacotranscriptomic approaches are powerful tools that leverage gene expression data for drug repurposing and treatment discovery in many diseases. Multiple databases attempt to connect human cellular transcriptional responses to small molecules for use in transcriptome-based drug discovery efforts.

Intensive pediatric chemotherapy regimen (PNET HR+5) in adult high-risk medulloblastoma and pineoblastoma patients.

Background: High-risk medulloblastoma (HRMB) is rare in adults. The 5-year overall survival rate is less than 60%. We present here a retrospective analysis of adults treated with an intensive pediatric chemo-radiotherapy regimen PNET HR + 5: NCT00936156.

Length of stay following elective craniotomy for tumor resection in children and young adults: a retrospective case series.

Purpose: Length of stay (LOS) is a critical metric of healthcare delivery. Prolonged LOS is associated with a heightened risk of adverse complications. We aimed to provide a comprehensive evaluation of LOS, specifically identifying variables associated with extended LOS (eLOS), in children and young adults following elective craniotomy for tumor resection.

Ezh2 Delays Activation of Differentiation Genes During Normal Cerebellar Granule Neuron Development and in Medulloblastoma.

Medulloblastoma (MB) is the most common malignant brain tumour in children. The Sonic Hedgehog (SHH)-medulloblastoma subtype arises from the cerebellar granule neuron lineage. Terminally differentiated neurons are incapable of undergoing further cell division, so an effective treatment for this tumour could be to force neuronal differentiation.

Utilization of Motor Imagery Training for Improvement of Balance of Ataxic Children after Medulloblastoma Resection.

This study investigated the effects of training using motor imagery on balance, gait parameters, and ataxia severity in children after they underwent medulloblastoma tumour resection. Fifty participated children, aged seven-nine years and diagnosed with cerebellar ataxia after medulloblastoma resection were selected from the Tumor Hospital of Cairo University. Two groups of patients were randomly divided: the study group and the control group.

High Expression of GABA Receptor β Subunit Genes Is Associated with Longer Overall Survival in Medulloblastoma.

Most of the rapid inhibitory neurotransmission in the brain is mediated through activation of the γ-aminobutyric acid (GABA) type A (GABA) receptor, which is a ligand-gated ion channel. GABA receptor activation via GABA binding allows for an intracellular influx of Cl ions, thus inducing cellular hyperpolarization. Each GABA receptor consists of a combination of five subunits, and several subunits have been proposed as biomarkers and therapeutic targets in cancer.