ATRT

Atypical teratoid/rhabdoid tumor (ATRT) is a rare childhood malignancy that originates in the central nervous system. Over ninety-five percent of ATRT patients have biallelic inactivation of the tumor suppressor gene SMARCB1 . ATRT has no standard treatment, and a major limiting factor in therapeutic development is the lack of reliable ATRT models. We employed CRISPR/Cas9 gene-editing technology to knock out SMARCB1 and TP53 genes in human episomal induced pluripotent stem cells (Epi-iPSCs), followed by brief neural induction, to generate an ATRT-like model...

Introduction Atypical teratoid rhabdoid tumor (ATRT) is among the most aggressive central nervous system malignancies. Although rare, this tumor typically afflicts young children and results in mortality within months. Here, we aim to determine key clinical features and treatment options that impact survival of patients with ATRT. Methods From the years 2000 to 2018, 363 patients with ATRT were identified from the Surveillance, Epidemiology, and End Results database. Univariate analysis was used to identify variables that had a significant impact on the primary endpoint of overall survival (OS)...

BCOR is expressed in a new brain tumour entity, i.e. 'CNS tumour with BCOR internal tandem duplication' (HGNET BCOR) but not in several other high grade paediatric brain tumours investigated. Immunohistochemical detection of BCOR expression may therefore serve as a potential diagnostic marker. Nevertheless, in rare paediatric glioma cases recurrent EP300-BCOR fusions were detected, which resulted in strong BCOR immunopositivity. We have therefore examined other, not analysed so far, types of central nervous system (CNS) tumours, pineoblastoma and germinoma, to assess a potential involvement of BCOR in these tumours...

Rhabdoid Tumor Predisposition Syndrome 1 (RTPS1) confers an increased risk of developing rhabdoid tumors and is caused by germline mutations in SMARCB1. RTPS1 should be evaluated in all individuals with rhabdoid tumor and is more likely in those with a young age at presentation (occasionally congenital presentation), multiple primary tumors, or a family history of rhabdoid tumor or RTPS1. Proband genetic testing is the standard method for diagnosing RTPS1. Most known RTPS1-related SMARCB1 gene mutations are copy number variants (CNVs) or single nucleotide variants/indels, but structural variant analysis (SVA) is not usually included in the molecular evaluation...

Solitary fibrous tumor/hemangiopericytoma (SFT/HPC) is a rare primary central nervous system (CNS) tumor, included in the World Health Organization (WHO) 2016 classification. Very few cases have been described in the literature so far, especially the infantile type. It is a mesenchymal tumor of the fibroblastic type, characterized by the fusion of NAB 2 and STAT 6 genes. A 10-month-old boy presented to our neurosurgery department with complaints of increasing head circumference since 1 month of age. The magnetic resonance imaging (MRI) showed a space-occupying lesion measuring 8...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

INTRODUCTION: Atypical teratoid/rhabdoid tumours (AT/RT) are malignant CNS tumours predominantly seen in infants and children. Adult AT/RTs have a predilection for mid-line structures, such as the pineal and pituitary glands. We report a case of AT/RT in a young adult, with its origin from the third ventricle. This is the first documented case of adult AT/RT in the third ventricle. CASE PRESENTATION: A 20-year-old male presented with acute onset headache and vomiting...

Atypical teratoid rhabdoid tumors (ATRT) are rare and aggressive embryonal tumors of central nervous system that typically affect children younger than 3 years of age. Given the generally poor outcomes of patients with ATRT and the significant toxicities associated with conventional multi-modal therapies, there is an urgent need for more novel approaches to treat ATRT, one such approach being immunotherapy. The recent rise of large-scale, multicenter interdisciplinary studies has delineated several molecular and genetic characteristics unique to ATRT...

Embryonal tumors (ETs) of the central nervous system (CNS) comprise a large heterogeneous group of highly malignant tumors that predominantly affect children and adolescents. Currently, the neoplasms classified as ET are the medulloblastoma (MB), embryonal tumors with multilayered rosettes (ETMR), medulloepithelioma (ME), CNS neuroblastoma (NB), CNS ganglioneuroblastoma (GNB), atypical teratoid/rhabdoid tumors (AT/RT), and CNS embryonal tumors with rhabdoid features. All these tumors are classified as malignant-grade IV neoplasms, and the prognosis of patients with these neoplasms is very poor...

The 2016 WHO classification of tumors of the central nervous system affected importantly the group of CNS embryonal tumors. Molecular analysis on methylome, genome, and transcriptome levels allowed better classification, identification of specific molecular hallmarks of the different subtypes of CNS embryonal tumors, and their more precise diagnosis. Routine application of appropriate molecular testing and standardized reporting are of pivotal importance for adequate prognosis and treatment, but also for epidemiology studies and search for efficient targeted therapies...

BACKGROUND: Liquid biopsies are revolutionary tools used to detect tumor-specific genetic alterations in body fluids, including the use of cell-free DNA (cfDNA) for molecular diagnosis in cancer patients. In brain tumors, cerebrospinal fluid (CSF) cfDNA might be more informative than plasma cfDNA. Here, we assess the use of CSF cfDNA in pediatric embryonal brain tumors (EBT) for molecular diagnosis. METHODS: The CSF cfDNA of pediatric patients with medulloblastoma ( n = 18), ATRT ( n = 3), ETMR ( n = 1), CNS NB FOXR2 ( n = 2) and pediatric EBT NOS ( n = 1) (mean cfDNA concentration 48 ng/mL; range 4-442 ng/mL) and matched tumor genomic DNA were sequenced by WES and/or a targeted sequencing approach to determine single-nucleotide variations (SNVs) and copy number alterations (CNA)...

BACKGROUND: Embryonal tumors are highly malignant cancers of the central nervous system, with a relatively high incidence in infants and young children. Even with intensive multimodal treatment the prognosis of many types is guarded, and treatment related toxicity is significant. Recent advances in molecular diagnostics allowed the discovery of novel entities and inter-tumor subgroups, with opportunities for improved risk-stratification and treatment approaches. SUMMARY: Medulloblastomas separate into four distinct subgroups with distinct clinicopathologic characteristics, and data from recent clinical trials for newly diagnosed medulloblastoma supports subgroup-specific treatment approaches...

Posterior fossa atypical teratoid rhabdoid tumor (ATRT) is a rare childhood tumor usually associated with a dismal prognosis. Although upfront surgical gross total resection (GTR) has classically been the first line of treatment, new multimodal treatments, including two-stage surgery, are showing promising results in terms of overall survival (OS) and complication rate. We present a case of a 9-month-old child treated with two-staged surgery and chemotherapy. When deemed risky, multimodal treatments, including staged surgeries, can be a safe alternative to reduce surgical mortality and morbidity...

BACKGROUND: NCI-COG Pediatric MATCH assigns patients aged 1-21 years with refractory solid tumors, brain tumors, lymphomas, and histiocytic disorders to phase II trials of molecularly targeted therapies based on detection of pre-defined genetic alterations. Patients whose tumors harbored EZH2 mutations or loss of SMARCB1 or SMARCA4 by immunohistochemistry were treated with EZH2 inhibitor tazemetostat. METHODS: Patients received tazemetostat for 28-day cycles until disease progression or intolerable toxicity (max 26 cycles)...

PURPOSE: Radiotherapy (RT) is associated with improved survival in atypical teratoid/rhabdoid tumor (ATRT); however, optimal RT delivery is unknown. A meta-analysis was conducted for disseminated (M+) ATRT receiving focal or craniospinal radiation (CSI). METHODS: After abstract screening, 25 studies (1995-2020) contained necessary patient, disease, and radiation treatment information (N = 96). All abstract, full text, and data capture were independently double-reviewed...

Atypical teratoid/rhabdoid tumors (ATRTs) represent a rare, but aggressive pediatric brain tumor entity. They are genetically defined by alterations in the SWI/SNF chromatin remodeling complex members SMARCB1 or SMARCA4. ATRTs can be further classified in different molecular subgroups based on their epigenetic profiles. Although recent studies suggest that the different subgroups have distinct clinical features, subgroup-specific treatment regimens have not been developed thus far. This is hampered by the lack of pre-clinical in vitro models representative of the different molecular subgroups...

INTRODUCTION AND IMPORTANCE: Malignant rhabdoid tumor is a rare malignancy which occurs in children with limited cases reported. CASE PRESENTATION: We report a very rare primary intraperitoneal rhabdoid tumor in a 9-year-old female child. The only case was first reported in a 10-year old girl in 2014 (Nam et al., 2014 [1]). The diagnostic became a problem as the case was initially diagnosed as Ovarian Malignancy. It did not match the initial abdominal Computed Tomography (CT) imaging which showed a bilateral malignant ovarian tumor that resembled Ovarian Carcinoma...

PURPOSE: Atypical teratoid/rhabdoid tumors (ATRT) of the central nervous system (CNS) are rare tumors with a poor prognosis and variable use of either focal or craniospinal (CSI) radiotherapy (RT). Outcomes on the prospective Pediatric Proton/Photon Consortium Registry (PPCR) were evaluated according to RT delivered. METHODS: Pediatric patients receiving RT were prospectively enrolled on PPCR to collect initial patient, disease, and treatment factors as well as provide follow-up for patient outcomes...

BACKGROUND: Atypical teratoid rhabdoid tumors (ATRT) are highly aggressive pediatric brain tumors. The available treatments rely on toxic chemotherapy and radiotherapy, which themselves can cause poor outcomes in young patients. Poly (ADP-ribose) polymerases (PARP), multifunctional enzymes which play an important role in DNA damage repair and genome stability have emerged as a new target in cancer therapy. An FDA-approved drug screen revealed that Rucaparib, a PARP inhibitor, is important for ATRT cell growth...