Atypical teratoid/rhabdoid tumors in adult patients: CT and MR imaging features.
Ontology highlight
ABSTRACT:
SUBMITTER: Han L
PROVIDER: S-EPMC7964939 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Atypical teratoid rhabdoid tumor (ATRT) is an aggressive pediatric brain tumor with limited therapeutic options. The hypothesis for this study was that the Wnt pathway triggered by the Wnt5B ligand plays an important role in ATRT biology. To address this hypothesis, the role of WNT5B and other Wnt pathway genes was analyzed in ATRT tissues and ATRT primary cell lines.Transcriptome-sequencing analyses were performed using nanoString platforms, immunohistochemistry, Western blotting, quantitative reverse transcriptase PCR, immunoprecipitation, short interference RNA studies, cell viability studies, and drug dose response (DDR) assays.Our transcriptome-sequencing results of Wnt pathway genes from ATRT tissues and cell lines indicated that the WNT5B gene is significantly upregulated in ATRT samples compared with nontumor brain samples. These results also indicated a differential expression of both canonical and noncanonical Wnt genes. Imunoprecipitation studies indicated that Wnt5B binds to Frizzled1 and Ryk receptors. Inhibition of WNT5B by short interference RNA decreased the expression of FRIZZLED1 and RYK. Cell viability studies a indicated significant decrease in cell viability by inhibiting Frizzled1 receptor. DDR assays showed promising results with some inhibitors.These promising therapeutic options will be studied further before starting a translational clinical trial. The success of these options will improve care for these patients.
| S-EPMC4483069 | biostudies-literature
Project description:Atypical teratoid/rhabdoid tumors (AT/RTs) are lethal central nervous system tumors, which are primarily diagnosed in infants. Current treatments for AT/RTs include surgery, radiotherapy, and chemotherapy; these treatments have poor prognoses and challenging side effects. The pivotal genetic event in AT/RT pathogenesis comprises the inactivation of SMARCB1 or SMARCA4. Recent epigenetic studies have demonstrated mutual and subtype-specific epigenetic derangements that drive tumorigenesis; the exploitation of these potential targets might improve the dismal treatment outcomes of AT/RTs. This review aims to summarize the literature concerning targeted molecular therapies for pediatric AT/RTs.
| S-EPMC9218972 | biostudies-literature
Project description:Atypical teratoid/rhabdoid (AT/RT) tumors are the most common malignant brain tumor of infancy and have a poor prognosis. We have previously identified very high expression of LIN28A and/or LIN28B in AT/RT tumors and showed that AT/RT have corresponding increased expression of the mitogen-activated protein (MAP) kinase pathway. Binimetinib is a novel inhibitor of mitogen-activated protein kinase (MAP2K1 or MEK), and is currently in pediatric phase II clinical trials for low-grade glioma. We hypothesized that binimetinib would inhibit growth of AT/RT cells by suppressing the MAP kinase pathway. Binimetinib inhibited AT/RT growth at nanomolar concentrations. Binimetinib decreased cell proliferation and induced apoptosis in AT/RT cells and significantly reduced AT/RT tumor growth in flank xenografts. Our data suggest that MAP kinase pathway inhibition could offer a potential avenue for treating these highly aggressive tumors.
| S-EPMC7821707 | biostudies-literature
Project description:BACKGROUND: To describe therapeutic approaches in children with atypical Teratoid Rhabdoid Tumours (ATRT) in France. METHODS: Observational study including all children less than 18 years old diagnosed with ATRT in France between 2009 and 2011. RESULTS: Forty seven children were included in this retrospective study. Six patients received no curative treatment while forty-one patients had a curative project. Median age was 1.5 years (range 0-16). The disease was disseminated in 10 patients. Surgical resection was complete in 21 cases. Chemotherapy was administered in 41 children. Twenty-six patients received upfront Vincristine-Methotrexate (5g/m2 x 3) with intra-thecal Methotrexate, which was stopped in eleven patients: in four cases the disease progressed and in seven cases the toxicities were manageable. Fifteen children received different chemotherapy courses and in four of them the diseases progressed. Eight patients underwent second-look surgery. Radiotherapy was administered in 17 patients at a median time of 19 weeks (13-44) after diagnosis. High-dose chemotherapy (HDCT) was given in 9 children and maintenance therapy in 5 children, starting at respectively 35 and 42 weeks after diagnosis. Median follow-up was 26 months (0.6-47). Median time for progression was 5 months. Two-years overall survival was 32% + /-8%. Median survival was 8 months. DISCUSSION: The survival rate of children with ATRT remains poor, the addition of VM is easily manageable but its benefit remains uncertain. The disease progressed mostly before radiotherapy. Future trials should focus on the delay of radiotherapy and the benefit of HDCT.
| S-EPMC4046281 | biostudies-literature
Project description:Atypical teratoid/rhabdoid tumors (AT/RT) are highly aggressive, malignant tumors and are the most common malignant brain tumor in children under 6 months of age. Currently, there is no standard treatment for AT/RT. Recent studies have reported potential anti-tumoral properties of ribavirin, a guanosine analog and anti-viral molecule approved by the Food and Drug Administration for treatment of hepatitis C. We previously demonstrated that ribavirin inhibited glioma cell growth in vitro and in vivo. Based on these results and the fact that no pre-clinical model of ribavirin in AT/RT exists, we decided to investigate the effect of ribavirin on several human AT/RT cell lines (BT12, BT16, and BT37) both in vitro and in vivo. We provide evidence that ribavirin has a significant impact on AT/RT cell growth and increases cell cycle arrest and cell death, potentially through modulation of the eIF4E and/or EZH2 pathways. Interestingly, using scratch wound and transwell Boyden chamber assays, we observed that ribavirin also impairs AT/RT cell migration, invasion, and adhesion. Finally, we demonstrate that ribavirin significantly improves the survival of mice orthotopically implanted with BT12 cells. Our work establishes that ribavirin is effective against AT/RT by decreasing tumoral cell growth and dissemination and could represent a new therapeutic option for children with this deadly disease.
| S-EPMC5814281 | biostudies-literature
Project description:Atypical teratoid rhabdoid tumor (ATRT) is a rare, highly malignant central nervous system cancer arising in infants and younger children, historically considered to be homogeneous, monogenic, and incurable. Recent use of intensified therapies has modestly improved survival for ATRT; however, a majority of patients will still succumb to their disease. While ATRTs almost universally exhibit loss of SMARCB1 (BAF47/INI1/SNF5), recent whole genome, transcriptome, and epigenomic analyses of large cohorts reveal previously underappreciated molecular heterogeneity. These discoveries provide novel insights into how SMARCB1 loss drives oncogenesis and confer specific therapeutic vulnerabilities, raising exciting prospects for molecularly stratified treatment for patients with ATRT.
| S-EPMC7339881 | biostudies-literature
Project description:Atypical teratoid rhabdoid tumors (AT/RTs) are rare pediatric brain tumors characterized by bialleic loss of the SMARCB1 tumor suppressor gene. In contrast to pediatric AT/RT that has a simple genome, very little is known about the adult AT/RT genomic landscape. Using a combination of whole-exome sequencing and high-resolution SNP array in a single adult pituitary AT/RT, we identified a total of 47 non-synonymous mutations, of which 20 were predicted to cause non-conservative amino acid substitutions, in addition to a subclone of cells with trisomy 8. We suggest that adult AT/RT may not be markedly dissimilar to other adult brain tumors where mutations in a range of genes, reflecting the functional specialization of different brain regions, but including SMARCB1 inactivation, may be required for its pathogenesis.
| S-EPMC4617150 | biostudies-literature
Project description:Atypical teratoid/rhabdoid tumors (AT/RTs) are highly aggressive pediatric brain tumors characterized by the presence of rhabdoid cells and negative immunostaining for INI1 (BAF47). Histogenesis is unknown and diagnosis can be challenging because of their extreme morphological and immunophenotypic heterogeneity. Currently no signature markers other than INI1 loss have been identified. To search for possible candidate proteins of interest in AT/RTs, Affymetrix GeneChip microarrays were utilized to investigate nine AT/RTs vs. 124 other tumor samples. The most distinctive gene identified was claudin 6 (CLDN6), a key component of tight junctions. CLDN6 showed moderate or higher mRNA expression in eight of nine AT/RTs, with little to no expression in 114 of 115 other tumors. Average expression was 38-fold higher in AT/RTs vs. other samples. Immunohistochemical (IHC) staining of 33 tumor specimens found positive membrane staining in seven of seven AT/RTs, and was negative in 26 of 27 other brain tumor samples. Notably, none of the 16 medulloblastomas/primitive neuroectodermal tumors showed IHC staining for CLDN6. IHC staining results closely matched the level of mRNA expression detected by microarray. CLDN6 may be a useful positive marker to help further identify AT/RTs for diagnostic and treatment purposes.
| S-EPMC8094697 | biostudies-literature
Project description:Novel discoveries involving the evaluation of potential therapeutics are based on newly identified molecular targets for atypical teratoid rhabdoid tumors (ATRT), which are the most common form of infantile brain tumors. Central nervous system ATRTs are rare, aggressive, and fast growing tumors of the brain and spinal cord and carry a very poor prognosis. Currently, the standard of care for ATRT patients is based on surgical resection followed by systemic chemotherapy and radiotherapy, which result in severe side effects. As protein tyrosine kinases have proven to be actionable targets that reduce tumor growth in a number of cancers, we examined how inhibiting tyrosine kinases affected ATRT tumor growth. Here, we examine the therapeutic efficacy of the broad-spectrum tyrosine kinase inhibitor vatalanib in the treatment of ATRT. Vatalanib significantly reduced the growth of ATRT tumor cell lines, both in two-dimensional cell culture and in three-dimensional cell culture using a spheroid model. As vatalanib had a remarkable effect on the growth of ATRT, we decided to use a transcriptomic approach to therapy by examining new actionable targets, such as tyrosine kinases. Next-generation RNA-sequencing and NanoString data analysis showed a significant increase in PTK7 RNA expression levels in ATRT tumors. Inhibition of PTK7 by siRNA treatment significantly decreases the viability of ATRT patient-derived tumor cell lines.Implications: These studies provide the groundwork for future preclinical in vivo studies aiming to investigate the efficacy of PTK7 inhibition on ATRT tumor growth. Mol Cancer Res; 15(8); 973-83. ©2017 AACR.
| S-EPMC5594561 | biostudies-literature
Project description:BackgroundAtypical teratoid/rhabdoid tumors (AT/RTs) are highly malignant brain tumors with inactivation of the SMARCB1 gene, which play a critical role in genomic transcriptional control. In this study, we analyzed the genomic and transcriptomic profiles of human AT/RTs to discover new druggable targets.MethodsMultiplanar sequencing analyses, including whole exome sequencing (WES), single nucleotide polymorphism (SNP) arrays, array comparative genomic hybridization (aCGH), and whole transcriptome sequencing (RNA-Seq), were performed on 4 AT/RT tissues. Validation of a druggable target was conducted using AT/RT cell lines.ResultsWES revealed that the AT/RT genome is extremely stable except for the inactivation of SMARCB1. However, we identified 897 significantly upregulated genes and 523 significantly downregulated genes identified using RNA-Seq, indicating that the transcriptional profiles of the AT/RT tissues changed substantially. Gene set enrichment assays revealed genes related to the canonical pathways of cancers, and nucleophosmin (NPM1) was the most significantly upregulated gene in the AT/RT samples. An NPM1 inhibitor (NSC348884) effectively suppressed the viability of 7 AT/RT cell lines. Network analyses showed that genes associated with NPM1 are mainly involved in cell cycle regulation. Upon treatment with an NPM1 inhibitor, cell cycle arrest at G1 phase was observed in AT/RT cells.ConclusionsWe propose that NPM1 is a novel therapeutic target for AT/RTs.
| S-EPMC6714307 | biostudies-literature