MODERN METHODS OF DIAGNOSIS AND TREATMENT OF ATYPICAL TERATOID RHABDOID TUMORS CNS IN CHILDREN

2021 ◽  
Vol 100 (3) ◽  
pp. 120-129
Author(s):  
L.V. Olkhova ◽  
◽  
O.G. Zheludkova ◽  
Keyword(s):  
Multimodal Therapy ◽  
Chemoradiation Therapy ◽  
Malignant Neoplasms ◽  
Biallelic Mutation ◽  
Atypical Teratoid ◽  
Grade Of Malignancy ◽  
Atypical Teratoid Rhabdoid Tumors ◽  
Rhabdoid Tumors ◽  
Brain And Spinal Cord ◽  
The Brain

Atypical teratoid rhabdoid tumors (ATRT) of the CNS in children are a group of aggressive malignant neoplasms with extremely poor prognosis, and therefore these tumors are classified as IV (highest) grade of malignancy. At the time of diagnosis, 20% of patients are found to have metastasized to the brain and spinal cord. The pathogenesis of ATRT is based on the biallelic mutation of the SMARCB1 gene, more rarely SMARCA4 genes. Despite the use of intensive multimodal therapy, the survival rate of patients with ATRT remains low. Recently, several groups of scientists, based on epigenetic and transcriptional studies, have identified 3 molecular groups of ATRT with different therapeutic sensitivity to chemoradiation therapy and, accordingly, have a different prognosis of the disease. This article presents the current literature data on epidemiology, pathogenesis, clinic, diagnosis and therapy of patients with ATRT, and describes the directions of treatment.

scholarly journals ATRT-09. IDENTIFICATION OF HUB GENES IN ATYPICAL TERATOID/RHABDOID TUMORS BY MULTIPLE-MICROARRAY ANALYSIS

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii277-iii277
Author(s):  
Wei Liu ◽  
Yi Chai ◽  
Junhua Wang ◽  
Yuqi Zhang
Keyword(s):  
Gene Expression ◽  
Enrichment Analysis ◽  
Functional Enrichment ◽  
Malignant Neoplasms ◽  
Pathway Enrichment Analysis ◽  
Normal Brain ◽  
Hub Genes ◽  
Atypical Teratoid ◽  
Atypical Teratoid Rhabdoid Tumors ◽  
Rhabdoid Tumors

Abstract BACKGROUND Atypical teratoid/rhabdoid tumors (ATRT) are rare, highly malignant neoplasms arising in infants and young children. However, the biological basis of ATRTs remains poorly understood. In the present study, we employed integrated bioinformatics to investigate the hub genes and potential molecular mechanism in ATRT. METHODS Three microarray datasets, GSE35943, GSE6635 and GSE86574, were downloaded from Gene Expression Omnibus (GEO) which contained a total of 79 samples including 32 normal brain tissue samples and 47 ATRT samples. The RobustRankAggreg method was employed to integrate the results of these gene expression datasets to obtain differentially expressed genes (DEGs). The GO function and KEGG pathway enrichment analysis were conducted at the Enrichr database. The hub genes were screened according to the degree using Cytoscape software. Finally, transcription factor (TF) of hub genes were obtained by the NetworkAnalyst algorithm. RESULTS A total of 297 DEGs, consisting of 94 downregulated DEGs and 103 upregulated DEGs were identified. Functional enrichment analysis revealed that these genes were associated with cell cycle, p53 signaling pathway and DNA replication. Protein-protein interaction (PPI) network analysis revealed that CDK1, CCNA2, BUB1B, CDC20, KIF11, KIF20A, KIF2C, NCAPG, NDC80, NUSAP1, PBK, RRM2, TPX2, TOP2A and TTK were hub genes and these genes could be regulated by MYC, SOX2 and KDM5B according to the results of TF analysis. CONCLUSIONS Our study will improve the understanding of the molecular mechanisms and provide novel therapeutic targets for ATRT.

Prognosis of atypical teratoid rhabdoid tumors (AT/RT) treated with multimodal therapy protocols. Report of our series

Neurocirugía ◽  
2016 ◽  
Vol 27 (2) ◽  
pp. 87-94 ◽  
Author(s):  
Alfonso Valencia-Moya ◽  
Laura González-García ◽  
Bienvenido Ros-López ◽  
Tomás Acha-García ◽  
Bernardo Weil-Lara ◽  
...  
Keyword(s):  
Multimodal Therapy ◽  
Atypical Teratoid ◽  
Atypical Teratoid Rhabdoid Tumors ◽  
Rhabdoid Tumors

scholarly journals Long-Term Remission of a Spinal Atypical Teratoid Rhabdoid Tumor in Response to Intensive Multimodal Therapy

2019 ◽  
Vol 2019 ◽  
pp. 1-4
Author(s):  
Fahd Refai ◽  
Haneen Al-Maghrabi ◽  
Hassan Al Trabolsi ◽  
Jaudah Al-Maghrabi
Keyword(s):  
Multimodal Therapy ◽  
Tumor Suppressor Protein ◽  
Central Nervous System Tumors ◽  
Histopathological Diagnosis ◽  
Atypical Teratoid Rhabdoid Tumor ◽  
Thoracic Spinal ◽  
Atypical Teratoid ◽  
Atypical Teratoid Rhabdoid Tumors ◽  
Rhabdoid Tumors

Atypical teratoid rhabdoid tumors (ATRTs) are rare and aggressive central nervous system tumors that infrequently arise in spinal locations in young children. Provided clinical and diagnostic suspicion is high, the histopathological diagnosis is relatively straightforward to secure by testing for the characteristic loss of the tumor suppressor protein SMARCB1/INI1. Here, we describe a case of thoracic spinal ATRT in a three-year-old boy that showed characteristic aggressive progression until managed with intensive multimodal therapy to achieve durable long-term remission. In doing so, we review the histopathological features, management, and current advances in molecular biology that hold promise for personalized ATRT therapy.

Clinical characteristics, treatment, and survival outcome in pediatric patients with atypical teratoid/rhabdoid tumors: a retrospective study by the Japan Children’s Cancer Group

2020 ◽  
Vol 25 (2) ◽  
pp. 111-120 ◽  
Author(s):  
Kai Yamasaki ◽  
Chikako Kiyotani ◽  
Keita Terashima ◽  
Yuko Watanabe ◽  
Masayuki Kanamori ◽  
...  
Keyword(s):  
Multimodal Therapy ◽  
Pediatric Patients ◽  
Positive Impact ◽  
Conditioning Regimen ◽  
High Dose ◽  
Primary Therapy ◽  
Female Ratio ◽  
Atypical Teratoid ◽  
Atypical Teratoid Rhabdoid Tumors ◽  
Rhabdoid Tumors

OBJECTIVEThe prognosis of atypical teratoid/rhabdoid tumors (ATRTs) has improved in recent years with the use of multimodal therapy, mainly in cases not involving metastatic disease. The authors wanted to obtain historical control data and evaluate the suitable treatments in Japanese children with ATRTs that were proven negative for INI-1 immunostaining.METHODSThe authors retrospectively collected clinical information on 38 pediatric patients with ATRTs treated from 2005 to 2016 and analyzed the data for this series.RESULTSThe median age of the patient population was 1.3 years, and the male/female ratio was approximately 2:1. Twenty-three patients (60.5%) had metastases. The effects of treatment on prognosis were analyzed for 34 patients after exclusion of 4 patients who could not receive curative treatment. At a median follow-up of 40.9 months, the mean (± SD) progression-free survival (PFS) and overall survival (OS) were 66.6% ± 8.3% and 45.9% ± 8.7% at 2 years and 44.2% ± 9.9% and 34.2% ± 8.9% at 5 years, respectively. The metastasis stage at diagnosis (M0–1 vs M2–4) (HR 2.68, 95% CI 1.08–6.65; p = 0.0338) and gross tumor resection (yes vs no) (HR 3.49, 95% CI 1.01–12.1; p = 0.0481) were prognostic factors for PFS but not for OS. Postoperative chemotherapy was performed in all 34 cases. High-dose chemotherapy was performed in 19 (55.8%) of 34 patients and showed a positive impact on OS (HR 0.31, 95% CI 0.11–0.86; p = 0.0254); the most commonly used regimen was a double-conditioning regimen of thiotepa plus melphalan. Local radiotherapy had a positive impact on both PFS and OS; however, craniospinal irradiation (CSI) performed in 12 patients as the primary therapy was associated with a poor outcome. Disseminated recurrence within 12 months from diagnosis was the most common pattern of treatment failure regardless of CSI.CONCLUSIONSThere has been an improvement in outcomes for pediatric ATRT patients since the introduction of multimodal therapy in Japan, mainly in patients without metastases. Even if selection bias is taken into consideration, CSI did not contribute to an improved prognosis. Novel treatment approaches are required for pediatric ATRT patients with metastases.

scholarly journals Atypical teratoid-rhabdoid tumors: molecular genetics feutures, perspectives of treatment. Review of literature

2020 ◽  
Vol 7 (1) ◽  
pp. 41-50
Author(s):  
A. Yu. Smirnova ◽  
A. Yu. Goncharov ◽  
Yu. V. Dinikina ◽  
A. V. Kim ◽  
W. A. Khachatryan ◽  
...  
Keyword(s):  
High Dose Chemotherapy ◽  
Monogenic Disease ◽  
Molecular Characteristics ◽  
Intrathecal Therapy ◽  
High Dose ◽  
Biallelic Mutation ◽  
Conventional Dose ◽  
Atypical Teratoid ◽  
Atypical Teratoid Rhabdoid Tumors ◽  
Rhabdoid Tumors

Atypical teratoid rhabdoid tumors (ATRT) are the most common malignant embryonal tumors of central nervous system in young children. Metastatic stage reveals in 20–30 % cases at the diagnosis. ATRT is a primarily monogenic disease characterized by the biallelic mutation of the SMARCB1, more rarely SMARCA4 genes. The survival rate of ATRT’s patients is poor. Multimodal treatment approaches including surgery, conventional dose chemotherapy with intrathecal therapy, high-dose chemotherapy with autologous stem cell resсue and radiotherapy have shown significant potential for improving outcomes. Recent epigenetic and transcriptional studies conducted by two independent research groups have identified three subgroups of ATRT. It has different molecular characteristics with appropriate therapeutic sensitivity. Further study of molecular types, inclusion of biologically targeted agents may be a promising strategy for optimizing treatment in future studies.

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