ZIC1 is a context-dependent medulloblastoma driver in the rhombic lip.

Transcription factors are frequent cancer driver genes, exhibiting noted specificity based on the precise cell of origin. We demonstrate that ZIC1 exhibits loss-of-function (LOF) somatic events in group 4 (G4) medulloblastoma through recurrent point mutations, subchromosomal deletions and mono-allelic epigenetic repression (60% of G4 medulloblastoma). In contrast, highly similar SHH medulloblastoma exhibits distinct and diametrically opposed gain-of-function mutations and copy number gains (20% of SHH medulloblastoma).

Prognostic Role of Invasion-Related Extracellular Matrix Molecules in Diffusely Infiltrating Grade 2 and 3 Astrocytomas.

Background: Astrocytoma, an IDH-mutant is a common primary brain tumor. Total surgical resection is not feasible due to peritumoral infiltration mediated by extracellular matrix (ECM) molecules.

Methods: This study aimed at determining the expression pattern of ECM molecules in different prognostic groups of WHO grade 2 and grade 3 patients and identifying the effect of onco-radiotherapy on tumor cell invasion of grade 3 patients.

Astrocyte- and NMDA receptor-dependent slow inward currents differently contribute to synaptic plasticity in an age-dependent manner in mouse and human neocortex.

Slow inward currents (SICs) are known as excitatory events of neurons elicited by astrocytic glutamate via activation of extrasynaptic NMDA receptors. By using slice electrophysiology, we tried to provide evidence that SICs can elicit synaptic plasticity. Age dependence of SICs and their impact on synaptic plasticity was also investigated in both on murine and human cortical slices.

MMP-9 as Prognostic Marker for Brain Tumours: A Comparative Study on Serum-Derived Small Extracellular Vesicles.

Matrix metalloproteinase-9 (MMP-9) degrades the extracellular matrix, contributes to tumour cell invasion and metastasis, and its elevated level in brain tumour tissues indicates poor prognosis. High-risk tissue biopsy can be replaced by liquid biopsy; however, the blood-brain barrier (BBB) prevents tumour-associated components from entering the peripheral blood, making the development of blood-based biomarkers challenging. Therefore, we examined the MMP-9 content of small extracellular vesicles (sEVs)-which can cross the BBB and are stable in body fluids-to characterise tumours with different invasion capacity.

Mapping the functional expression of auxiliary subunits of K1.1 in glioblastoma.

Glioblastoma (GBM) is the most aggressive glial tumor, where ion channels, including K1.1, are candidates for new therapeutic options. Since the auxiliary subunits linked to K1.

Mitochondrial DNA copy number changes, heteroplasmy, and mutations in plasma-derived exosomes and brain tissue of glioblastoma patients.

Glioblastoma is the most common malignant tumor of the central nervous system (CNS) in adults. Glioblastoma cells show increased glucose consumption associated with poor prognosis. Since mitochondria play a crucial role in energy metabolism, mutations and copy number changes of mitochondrial DNA may serve as biomarkers.

Topographic mapping of the glioblastoma proteome reveals a triple-axis model of intra-tumoral heterogeneity.

Glioblastoma is an aggressive form of brain cancer with well-established patterns of intra-tumoral heterogeneity implicated in treatment resistance and progression. While regional and single cell transcriptomic variations of glioblastoma have been recently resolved, downstream phenotype-level proteomic programs have yet to be assigned across glioblastoma's hallmark histomorphologic niches. Here, we leverage mass spectrometry to spatially align abundance levels of 4,794 proteins to distinct histologic patterns across 20 patients and propose diverse molecular programs operational within these regional tumor compartments.

Novel Concepts of Glioblastoma Therapy Concerning Its Heterogeneity.

Although treatment outcomes of glioblastoma, the most malignant central nervous system (CNS) tumor, has improved in the past decades, it is still incurable, and survival has only slightly improved. Advances in molecular biology and genetics have completely transformed our understanding of glioblastoma. Multiple classifications and different diagnostic methods were made according to novel molecular markers.

Analysis of Circulating miRNA Profile in Plasma Samples of Glioblastoma Patients.

(1) Background: Glioblastoma multiforme (GBM) is among the most aggressive cancers with a poor prognosis. Treatment options are limited, clinicians lack efficient prognostic and predictive markers. Circulating miRNAs-besides being important regulators of cancer development-may have potential as diagnostic biomarkers of GBM.

Raman Spectral Signatures of Serum-Derived Extracellular Vesicle-Enriched Isolates May Support the Diagnosis of CNS Tumors.

Investigating the molecular composition of small extracellular vesicles (sEVs) for tumor diagnostic purposes is becoming increasingly popular, especially for diseases for which diagnosis is challenging, such as central nervous system (CNS) malignancies. Thorough examination of the molecular content of sEVs by Raman spectroscopy is a promising but hitherto barely explored approach for these tumor types. We attempt to reveal the potential role of serum-derived sEVs in diagnosing CNS tumors through Raman spectroscopic analyses using a relevant number of clinical samples.

The transcriptional landscape of Shh medulloblastoma.

Sonic hedgehog medulloblastoma encompasses a clinically and molecularly diverse group of cancers of the developing central nervous system. Here, we use unbiased sequencing of the transcriptome across a large cohort of 250 tumors to reveal differences among molecular subtypes of the disease, and demonstrate the previously unappreciated importance of non-coding RNA transcripts. We identify alterations within the cAMP dependent pathway (GNAS, PRKAR1A) which converge on GLI2 activity and show that 18% of tumors have a genetic event that directly targets the abundance and/or stability of MYCN.

[The role of low grade glioma prognostic factors in therapeutic choices - summary of international literature and recommendations with conclusions].

Our knowledge on low grade gliomas has grown extensively recently. Both molecular alterations and clinical trials unraveling their clinical significance are difficult to get familiar with. Thus, efforts made to reach any consensus are of upmost importance, so that multidisciplinary teams involved in patient management can make up-to-date, individually-tailored therapeutic plans.

Histone H3.3G34-Mutant Interneuron Progenitors Co-opt PDGFRA for Gliomagenesis.

Histone H3.3 glycine 34 to arginine/valine (G34R/V) mutations drive deadly gliomas and show exquisite regional and temporal specificity, suggesting a developmental context permissive to their effects. Here we show that 50% of G34R/V tumors (n = 95) bear activating PDGFRA mutations that display strong selection pressure at recurrence.

Novel Molecular Markers in Glioblastoma-Benefits of Liquid Biopsy.

Glioblastoma is a primary Central Nervous System (CNS) malignancy with poor survival. Treatment options are scarce and despite the extremely heterogeneous nature of the disease, clinicians lack prognostic and predictive markers to characterize patients with different outcomes. Certain immunohistochemistry, FISH, or PCR-based molecular markers, including isocitrate dehydrogenase1/2 (IDH1/2) mutations, epidermal growth factor receptor variant III (EGFRvIII) mutation, vascular endothelial growth factor overexpression (VEGF) overexpression, or (O6-Methylguanine-DNA methyltransferase promoter) MGMT promoter methylation status, are well-described; however, their clinical usefulness and accuracy is limited, and tumor tissue samples are always necessary.

[Prognostic significance of invasion in glioblastoma].

Background And Purpose: Glioblastoma is the most common malignant CNS tumor, its surgical removal is hindered by the tumors invasive nature, while current anti-tumor therapies show limited effectiveness - mean overall survival is 16-24 months. Some patients show minimal response towards standard oncotherapy, however there are no routinely available prognostic and predictive markers in clinical practice to identify the background of mentioned differences in prognosis. This research aims to identify the prognostic significance of invasion-related extracellular (ECM) components.

Small Extracellular Vesicles Isolated from Serum May Serve as Signal-Enhancers for the Monitoring of CNS Tumors.

Liquid biopsy-based methods to test biomarkers (e.g., serum proteins and extracellular vesicles) may help to monitor brain tumors.

Prognosis and Treatment Outcomes of Patients Undergoing Resection of Brain Metastases from Breast Cancer.

Background: Brain metastases from breast cancer have poor prognosis and are a challenge to treat. Multiple treatment options are available. Descriptive and prognostic data on breast cancer brain metastases is limited.

Recurrent noncoding U1 snRNA mutations drive cryptic splicing in SHH medulloblastoma.

In cancer, recurrent somatic single-nucleotide variants-which are rare in most paediatric cancers-are confined largely to protein-coding genes. Here we report highly recurrent hotspot mutations (r.3A>G) of U1 spliceosomal small nuclear RNAs (snRNAs) in about 50% of Sonic hedgehog (SHH) medulloblastomas.

Influence of Oncotherapy and Clinical Parameters on Survival of Glioblastoma Patients: A Single Center Experience.

Background: Routine administration of temozolomide (TMZ) in the treatment protocol of glioblastoma in the last few years resulted in improving survival parameters of these patients but efficacy of supplementary bevacizumab (BVC) monotherapy has not been evidently proven. In this study, the effectiveness of different postoperative therapy for glioblastoma patients treated in our institute was evaluated. In addition, the prognostic value of clinical parameters on survival was also analyzed.

Significance of liquid biopsy in glioblastoma - A review.

Glioblastoma (GBM) is the most common and most aggressive primary malignant brain tumor with a 16-24 -months overall survival time (OS). Effective management is hindered by intratumoral heterogeneity, a characteristic trait of GBM which results in subpopulations of cells with altered therapeutic responsiveness, different invasiveness and growth potential. Correct initial molecular profiling of the tumor, as well as following its molecular biological changes are further impeded by the intracranial location of the tumors, hence the risks of surgical interventions.

Extracellular matrix differences in glioblastoma patients with different prognoses.

Glioblastoma is the most common malignant central nervous system tumor. Patient outcome remains poor despite the development of therapy and increased understanding of the disease in the past decades. Glioma cells invade the peritumoral brain, which results in inevitable tumor recurrence.

The Expressional Pattern of Invasion-Related Extracellular Matrix Molecules in CNS Tumors.

Astrocytomas are primary CNS malignancies which infiltrate the peritumoral tissue, even when they are low-grade. Schwannomas are also primary CNS tumors, however, they do not show peritumoral infiltration similarly to brain metastases which almost never invade the neighboring parts of brain. Extracellular matrix is altered in composition in various cancer types and is proposed to play an important role in the development of invasiveness of astrocytic tumors.

Heterogeneity within the PF-EPN-B ependymoma subgroup.

Posterior fossa ependymoma comprise three distinct molecular variants, termed PF-EPN-A (PFA), PF-EPN-B (PFB), and PF-EPN-SE (subependymoma). Clinically, they are very disparate and PFB tumors are currently being considered for a trial of radiation avoidance. However, to move forward, unraveling the heterogeneity within PFB would be highly desirable.

Differences in Extracellular Matrix Composition and its Role in Invasion in Primary and Secondary Intracerebral Malignancies.

Background/aim: The most common malignant primary brain tumor is glioblastoma which infiltrates the peritumoral brain, while secondary brain metastases are well demarcated malignancies. Previous research has proved the pivotal role of the changes in the extracellular matrix (ECM) in cancer cell invasion.

Materials And Methods: The mRNA expression of 40 ECM molecules was determined using qRT-PCR in 54 fresh-frozen glioblastoma and brain metastasis samples.