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Medulloblastoma - Europe PMC

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Last Updated: 24 September 2022

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Failure of human rhombic lip differentiation underlies medulloblastoma formation.

In the upper rhombic lip granule cell lineage 5-8, Mutations that initiate Sonic hedgehog signaling lead to Sonic hedgehog MB. Here we show that somatic mutations that cause G4 MB converge on the key binding factor alpha complex and mutually exclusive variants that affect CBFA2T2, CBFA2T3, PRDM6, UTX, and OTX2. Early in the cerebellar RL subventricular zone in Homo sapiens, CBFA2T2 is expressed early, and G4 MB transcriptionally resembles these progenitors but is stalled in developmental development. This differentiation blockade is removed by OTX2 models' knockdown, which allows MB cells to spontaneously progress along normal developmental differentiation trajectories. The split human RL, which is expected to produce most of the neurons in the human brain, and the high number of susceptible EOMES + KI67 + unipolar forest cell progenitor cells may have contributed to our species's onset of G4 MB development.

Source link: https://europepmc.org/article/MED/36131014


Unified rhombic lip origins of group 3 and group 4 medulloblastoma.

Molecular signatures embedded within a human rhombic-lip-derived lineage trajectory linked to photoreceptor and unipolar forest cell expression profiles maintained in group 3 and group 4 medulloblastoma have been interpreted within a convergent framework, indicating a convergent basis. To the nodulus, a systematic diagnostic-imaging review of a prospective institutional cohort showed the putative anatomical sources of group 3 and group 4 tumours to the nodulus. Our findings connect the molecular and phenotypic characteristics of clinically battling medulloblastoma subgroups of the rhombic lip in the early stages of human evolution's development.

Source link: https://europepmc.org/article/MED/36131015


Parent ratings of executive functioning in pediatric survivors of medulloblastoma and pilocytic astrocytoma.

The present research compared parent-rated executive of pediatric medulloblastoma and pilocytic astrocytoma survivors. Although medical care for both animals includes surgical resection, children with MB also receive chemotherapy and craniospinal irradiation, according to the publication. The Behavior Rating Inventory of Executive Functioning of 36 MB survivors and 20 PA survivors of 36 MB survivors and 20 PA residents completed the Behavior Rating Inventory of Executive Functioning. The PA group, on the MB group, was expected to have significant difficulties on all BRIEF scales, except the Shift scale. Also, all mean BRIEF scores for MB survivors were within normal ranges, except for Organization of Materials, which were significantly different from normative norms. Overall, PA survivors were rated as having poorer executive function than MB survivors, despite this. The BRIEF's parent questionnaires may have real-world consequences for pediatric brain tumor survivors.

Source link: https://europepmc.org/article/MED/36111630


Clinically applicable 39 genes targeted mutational analysis predicts recurrence in pediatric medulloblastoma: a monocenter cohort study

We set out to identify a gene mutation pattern for individual recurrent risk assessment patients with medulloblastoma. Methods The results of this monocenter cohort study were analyzed for clinical outcomes, including anatomic and temporal distributions of relapse and post-recurrence survival. Using a panel of 39 genes to design a gene classifier using an elastic net regression scheme, a genetic database of 39 genes was tested. Results A total of 23 of 118 patients experienced recurrence, with a large number of patients in the extremely high risk group. The majority of patients had some distal disease 56%. Patients were categorized into high and low risk groups by a recurrent gene signature for medulloblastoma that contained 27 genes. Patients with elevated recurrence risk scores had shorter recurrence-free survival and overall survival than patients with lower risk scores. The recurrent score is a reliable prognostic tool for recurrence in patients with medulloblastoma.

Source link: https://europepmc.org/article/PPR/PPR545615


Craniospinal irradiation high dose as independent predictor of permanent alopecia in childhood medulloblastoma survivors: cohort study and literature review

Patients were divided into three groups based on the craniospinal irradiation dose received and defined permanent alopecia first in terms of the skin region affected then based on the toxicity degree. Both groups' hair loss was found to be independent of alopecia of the whole skin and in the nape region. At multivariate analysis, neither in permanent hair loss of the whole skin nor just in the nuchal area, the posterior cranial fossa booster volume and dose were not significant. Acute injury to the hair follicle is dose dependent, but in terms of late side effects, constant and homogeneous daily radiation of a large volume may have a greater effect than a larger but focal dose of radiotherapy.

Source link: https://europepmc.org/article/PPR/PPR544296


Incidence and risk factors for necessitating shunting following medulloblastoma surgery in Children: a monocenter, retrospective, observational cohort study

Purpose: Following resection, there have been insufficient records for pediatric patients with medulloblastoma, which necessitates shunting. This research aims to determine which characters are related to the occurrence in this patient subset. Methods: We surveyed this monocenter, retrospective, observational cohort of patients who underwent medulloblastoma resection at our hospital from July 1, 2010 to August 1, 2021. The incidence of necessitating permanent shunts was 25. 6%. The length of manifestations can be a covariate of tumor volume and elevated risk of shunt use. In addition, tumor size was a possible predictor in patients with sub-resection. Finally, there was no significant difference between the distribution of molecular subgroups for necessitating permanent shunt patients. Conclusion: With the medulloblastoma invasion, the incidence was heightened. In all patients, there was not a sufficient number of postresection hydrocephalus in patients with medulloblastoma to cause a prophylactic permanent shunt.

Source link: https://europepmc.org/article/PPR/PPR544611


Compartments in medulloblastoma with extensive nodularity are connected through differentiation along the granular precursor lineage

Cerbellar tumors with two histologically distinct compartments and varying disease course are the cause of widespread nodularity in Medulloblastoma with prominent nodularity. Cells with an astroglial phenotype were discovered in close proximity to migrating, late CGNP-like, and postmitotic neuronally differentiated cells. Our research reveals how spatial tissue organization is related to proliferating tumor cells' development from a migrating precursor stage to differentiated tumor cells with a more benign phenotype. We anticipate that our framework for integrating single nucleus RNA-sequencing and spatial transcriptomics will help to identify intercompartmental relationships in other cancers of varying histology.

Source link: https://europepmc.org/article/PPR/PPR540936


Miat and interacting protein Metadherin maintain a stem-like niche to promote medulloblastoma tumorigenesis and treatment resistance.

Miat is an lncRNA enriched in the sonic hedgehog group of MB that is required for the maintenance of a treatment-resistant stem-like phenotype in the condition. Loss of Miat: Tumor-initiating, stem-like MB cells cell differentiation is established in the differentiation of tumor-initiating, stem-like MB cells and ensures tumor differentiation of tumor-like MB cells into a nontumorigenic state. The expression of Miat in stem-like MB cells also aids in treatment resistance by down-regulating p53 signaling and impairing radiation-induced cell death, which can be reversed by therapeutic inhibition of Miat using antisense oligonucleotides.

Source link: https://europepmc.org/article/MED/36067288


Systematic analysis of MCM3 in pediatric medulloblastoma via multi-omics analysis.

Minichromosome maintenance proteins are DNA-dependent ATPases that bind to replication origins and allow for a single round of DNA replication. We used multi-omics data from the GEO database to analyze the mechanisms involved by aberrant MCM3 expression and determine its clinical relevance in cell lines and tumor samples in order to consistently determine the mechanisms involved in cell lines and tumor samples in order to properly determine their clinical significance. We first reported the upregulation of MCM3 in medulloblastoma at bulk and single-cell RNA sequence levels, showing the possibility of MCM3 to promote DNA replication. MCM3 dysregulation may have arisen from abnormal methylation of MCM3. In addition, we found that MCM3 expression was closely related to the IC 50 values of cisplatin and etoposide. Overall, our study found that MCM3 could be a potential biomarker with clinical relevance and better guidance than current histological and molecular classifications for clinical decision-making.

Source link: https://europepmc.org/article/MED/36133906


Developmental Basis of SHH Medulloblastoma Heterogeneity

Medulloblastoma is one of the most common malignant pediatric brain tumors. For 30% of MB cases, the sonic hedgehog subtype of the cerebellar cortex that differentiates into granule neurons is most common. We performed single-nucleus RNA-sequencing on seven highly differentiated SHH MB with extensive nodular histology and found malignant cells resembling each stage of granule neuron development, leading to this investigation. We connected these findings to existing research and discovered that established molecular subtypes of SHH MB are enriched for specific developmental cell types by using novel computational techniques.

Source link: https://europepmc.org/article/PPR/PPR539897

* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions

* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions