Choroid plexus tumors in adults: a retrospective mono-institutional study.

Purpose: Choroid plexus tumors (CPT) are rare entities, and even rarer in adulthood.

Methods: A retrospective consecutive series of 24 adult CPT patients was reviewed.

Results: We described 24 adult CPTs.

Clinicopathological and molecular landscape of 5-year IDH-wild-type glioblastoma survivors: A multicentric retrospective study.

Five-year glioblastoma (GBM) survivors (LTS) are the minority of the isocitrate dehydrogenase (IDH)-wild-type GBM patients, and their molecular fingerprint is still largely unexplored. This multicenter retrospective study analyzed a large LTS-GBM cohort from nine Italian institutions and molecularly characterized a subgroup of patients by mutation, DNA methylation (DNAm) and copy number variation (CNV) profiling, comparing it to standard survival GBM. Mutation scan allowed the identification of pathogenic variants in most cases, showing a similar mutational spectrum in both groups, and highlighted TP53 as the most commonly mutated gene in the LTS group.

Development of A Radiomic Model for Promoter Methylation Detection in Glioblastoma Using Conventional MRI.

The methylation of the O6-methylguanine-DNA methyltransferase () promoter is a molecular marker associated with a better response to chemotherapy in patients with glioblastoma (GB). Standard pre-operative magnetic resonance imaging (MRI) analysis is not adequate to detect promoter methylation. This study aims to evaluate whether the radiomic features extracted from multiple tumor subregions using multiparametric MRI can predict promoter methylation status in GB patients.

Expression analysis of NF1-mutated alleles in a rare compound heterozygous spinal NF1 patient by digital PCR.

Backgroud: Neurofibromatosis type 1 (NF1) is a heterogeneous neurocutaneous disorder. Spinal neurofibromatosis (SNF) is a distinct clinical entity of NF1, characterized by bilateral neurofibromas involving all spinal nerve roots. Although both forms are caused by intragenic heterozygous variants of NF1, missense variants have been associated with SNF, according to a dominant inheritance model causing haploinsufficiency.

European Cancer Organisation Essential Requirements for Quality Cancer Care: Adult glioma.

European Cancer Organisation Essential Requirements for Quality Cancer Care (ERQCCs) are explanations of the organisation and actions necessary to provide high-quality care to patients with a specific cancer type. They are compiled by a working group of European experts representing disciplines involved in cancer care, and provide oncology teams, patients, policymakers and managers with an overview of the essential requirements in any healthcare system. The focus here is on adult glioma.

New insights into the molecular basis of spinal neurofibromatosis type 1.

Spinal neurofibromatosis (SNF) is a form of neurofibromatosis type 1 (NF1) characterized by bilateral neurofibromas involving all spinal roots. The pathogenic mechanisms determining the SNF form are currently unknown. To verify the presence of genetic variants possibly related to SNF or classic NF1, we studied 106 sporadic NF1 and 75 SNF patients using an NGS panel of 286 genes encoding RAS pathway effectors and neurofibromin interactors and evaluated the expression of syndecans (SDC1, SDC2, SDC3, SDC4), the NF1 3' tertile interactors, by quantitative real-time PCR.

Cognitive and Behavioral Outcome of Pediatric Low-Grade Central Nervous System Tumors Treated Only with Surgery: A Single Center Experience.

Background: The present mono-institutional report aimed to describe the cognitive and behavioral outcomes of low-grade central nervous system (CNS) tumors in a cohort of children treated exclusively with surgical intervention.

Methods: Medical records from 2000-2020 were retrospectively analyzed. We included 38 children (mean age at first evaluation 8 years and 3 months, 16 females) who had undergone presurgical cognitive-behavioral evaluation and/or at least 6 months follow-up.

Genome-wide profiling of patient-derived glioblastoma stem-like cells reveals recurrent genetic and transcriptomic signatures associated with brain tumors.

Purpose: Patient-derived cancer cell lines can be very useful to investigate genetic as well as epigenetic mechanisms of transformation and to test new drugs. In this multi-centric study, we performed genomic and transcriptomic characterization of a large set of patient-derived glioblastoma (GBM) stem-like cells (GSCs).

Methods: 94 (80 I surgery/14 II surgery) and 53 (42 I surgery/11 II surgery) GSCs lines underwent whole exome and trascriptome analysis, respectively.

CSF-based liquid biopsy pointing to a diagnosis of diffuse glioma in a patient with supposed neurodegenerative disorder.

Introduction: The differential diagnosis of brain diseases becomes challenging in cases where imaging is not sufficiently informative, and surgical biopsy is impossible or unacceptable to the patient.

Methods: An elderly patient with progressive short-term memory loss and cognitive impairment presented with a normal brain CT scan, a brain FDG-PET that indicated symmetrical deterioration of the white matter in the frontal lobes, and inconclusive results of a molecular marker analysis of suspected dementia in cerebrospinal fluid (CSF). Brain MRI suggested the diagnosis of lower grade glioma.

Sporadic spinal psammomatous malignant melanotic nerve sheath tumor: A case report and literature review.

Background: Sporadic Spinal Psammomatous Malignant Melanotic Nerve Sheath Tumor (SSP-MMNST) is a rare subgroup of peripheral nerve sheath tumors arising along the spine. Only a few reports of SSP-MMNST have been described. In this paper, we review the literature on SSP-MMNST focusing on clinical, and diagnostic features, as well as investigating possible pathogenetic mechanisms to better implement therapeutic strategies.

Involvement of GABAergic Interneuron Subtypes in 4-Aminopyridine-Induced Seizure-Like Events in Mouse Entorhinal Cortex .

Single-unit recordings performed in temporal lobe epilepsy patients and in models of temporal lobe seizures have shown that interneurons are active at focal seizure onset. We performed simultaneous patch-clamp and field potential recordings in entorhinal cortex slices of GAD65 and GAD67 C57BL/6J male mice that express green fluorescent protein in GABAergic neurons to analyze the activity of specific interneuron (IN) subpopulations during acute seizure-like events (SLEs) induced by 4-aminopyridine (4-AP; 100 μm). IN subtypes were identified as parvalbuminergic (IN, = 17), cholecystokinergic (IN), = 13], and somatostatinergic (IN, = 15), according to neurophysiological features and single-cell digital PCR.

LZTR1 Mutation Mediates Oncogenesis through Stabilization of EGFR and AXL.

Unlabelled: LZTR1 is the substrate-specific adaptor of a CUL3-dependent ubiquitin ligase frequently mutated in sporadic and syndromic cancer. We combined biochemical and genetic studies to identify LZTR1 substrates and interrogated their tumor-driving function in the context of LZTR1 loss-of-function mutations. Unbiased screens converged on EGFR and AXL receptor tyrosine kinases as LZTR1 interactors targeted for ubiquitin-dependent degradation in the lysosome.

Characterization of 22q12 Microdeletions Causing Position Effect in Rare NF2 Patients with Complex Phenotypes.

Neurofibromatosis type 2 is an autosomal dominant tumor-prone disorder mainly caused by point mutations or intragenic deletions. Few individuals with a complex phenotype and 22q12 microdeletions have been described. The 22q12 microdeletions' pathogenic effects at the genetic and epigenetic levels are currently unknown.

High tumor mutational burden and T-cell activation are associated with long-term response to anti-PD1 therapy in Lynch syndrome recurrent glioblastoma patient.

Background: Glioblastomas (GBMs) in patients harboring somatic or germinal mutations of mismatch-repair (MMR) genes exhibit a hypermutable phenotype. Here, we describe a GBM patient with increased tumor mutational burden and germline MMR mutations, treated using anti-PD1 therapy.

Methods: A woman with newly diagnosed GBM (nGBM) was treated by surgery, radiotherapy, and temozolomide.

Expansion of effector and memory T cells is associated with increased survival in recurrent glioblastomas treated with dendritic cell immunotherapy.

Background: The efficacy of dendritic cell (DC) immunotherapy as a single therapeutic modality for the treatment of glioblastoma (GBM) patients remains limited. In this study, we evaluated in patients with GBM recurrence the immune-mediated effects of DC loaded with autologous tumor lysate combined with temozolomide (TMZ) or tetanus toxoid (TT).

Methods: In the phase I-II clinical study DENDR2, 12 patients were treated with 5 DC vaccinations combined with dose-dense TMZ.

Simultaneous Detection of , , , and Gene Mutations by Targeted NGS in an Italian Cohort of Suspected NF1 Patients.

Neurofibromatosis type 1 (NF1) displays overlapping phenotypes with other neurocutaneous diseases such as Legius Syndrome. Here, we present results obtained using a next generation sequencing (NGS) panel including , , , , and genes on Ion Torrent. Together with NGS, the Multiplex Ligation-Dependent Probe Amplification Analysis (MLPA) method was performed to rule out large deletions/duplications in gene; we validated the MLPA/NGS approach using Sanger sequencing on DNA or RNA of both positive and negative samples.

Clinical, molecular, and radiomic profile of gliomas with FGFR3-TACC3 fusions.

Background: Actionable fibroblast growth factor receptor 3 (FGFR3)-transforming acidic coiled-coil protein 3 fusions (F3T3) are found in approximately 3% of gliomas, but their characteristics and prognostic significance are still poorly defined. Our goal was to characterize the clinical, radiological, and molecular profile of F3T3 positive diffuse gliomas.

Methods: We screened F3T3 fusion by real-time (RT)-PCR and FGFR3 immunohistochemistry in a large series of gliomas, characterized for main genetic alterations, histology, and clinical evolution.

Gliomatosis cerebri (GC) or GC-like? A picture to be reconsidered in neuro-oncology based on large retrospective analysis of GC series.

Introduction: Gliomatosis cerebri (GC), defined until 2016 as a distinct astrocytic glioma entity, has been removed from the 2016 World Health Organization classification of tumors of the central nervous system. However, its identity is still debated.

Materials And Methods: We retrospectively present 122 patients, including a subgroup with histology confirmation (n = 75, cohort b).

The Search for Molecular Markers in a Gene-Orphan Case Study of a Pediatric Spinal Cord Pilocytic Astrocytoma.

Background/aim: We herein presented a case of pediatric spinal cord pilocytic astrocytoma diagnosed on the basis of histopathological and clinical findings.

Materials And Methods: Given the paucity of data on genetic features for this tumor, we performed exome, array CGH and RNA sequencing analysis from nucleic acids isolated from a unique and not repeatable very small amount of a formalin-fixed, paraffin-embedded (FFPE) specimen.

Results: DNA mutation analysis, comparing tumor and normal lymphocyte peripheral DNA, evidenced few tumor-specific single nucleotide variants in DEFB119, MUC5B, NUDT1, LTBP3 and CPSF3L genes.

In vivo 2-hydroxyglutarate-proton magnetic resonance spectroscopy (3 T, PRESS technique) in treatment-naïve suspect lower-grade gliomas: feasibility and accuracy in a clinical setting.

Unlabelled: Isocitrate dehydrogenase 1/2 (IDH1/2) mutations are often detected in lower-grade gliomas (LGG) and result into 2-hydroxyglutarate (2HG) synthesis. Prior studies showed that 2HG can be detected in vivo using magnetic resonance spectroscopy (MRS), but its accuracy and translational impact are still under investigation.

Purpose: To investigate the clinical feasibility of MRS for in vivo detection and quantification of 2HG on consecutive treatment-naïve suspect LGG patients and to compare MRS accuracy with tissue IDH1/2 analysis.

Survival gain in glioblastoma patients treated with dendritic cell immunotherapy is associated with increased NK but not CD8 T cell activation in the presence of adjuvant temozolomide.

In a two-stage phase II study, 24 patients with first diagnosis of glioblastoma (GBM) were treated with dendritic cell (DC) immunotherapy associated to standard radiochemotherapy with temozolomide (TMZ) followed by adjuvant TMZ. Three intradermal injections of mature DC loaded with autologous GBM lysate were administered before adjuvant TMZ, while 4 injections were performed during adjuvant TMZ. According to a two-stage Simon design, to proceed to the second stage progression-free survival (PFS) 12 months after surgery was expected in at least 8 cases enrolled in the first stage.