Spontaneous Regression of Atypical Teratoid Rhabdoid Tumor Without Therapy in a Patient With Uncommon Regional Inactivation of SMARCB1 (hSNF5/INI1)

2018 ◽  
Vol 22 (2) ◽  
pp. 161-165 ◽  
Author(s):  
Jo Elle G Peterson ◽  
Abhishek Bavle ◽  
Vidya P Mehta ◽  
Ronald A Rauch ◽  
William E Whitehead ◽  
...  
Keyword(s):  
Spontaneous Regression ◽  
Tumor Regression ◽  
Rhabdoid Tumor ◽  
Molecular Heterogeneity ◽  
Central Nervous System Tumor ◽  
Atypical Teratoid Rhabdoid Tumor ◽  
Intact Cells ◽  
Truncating Mutation ◽  
Rhabdoid Cells ◽  
Atypical Teratoid

Atypical teratoid/rhabdoid tumor (ATRT) is a high-grade central nervous system tumor, with poor prognosis despite intensive multimodal therapy. Loss of nuclear immunostaining for INI1 due to inactivation of the hSNF5/INI1 tumor suppressor gene is pathognomonic of ATRT. We present a patient with congenital ATRT, who had spontaneous tumor regression without therapy, and is disease-free 4 years later. Tumor histopathology showed rhabdoid cells characteristic of ATRT, but immunohistochemistry revealed heterogeneous loss of nuclear INI1 staining. The populations of INI1-intact and INI1-deficient cells were separated by laser microdissection, for molecular analysis with DNA sequencing and fluorescence in situ hybridization. The INI1-negative cells were found to harbor a heterozygous deletion and truncating mutation of the hSNF5/INI1 locus, while the INI1-intact cells had 2 copies of the wild-type INI1 gene. To our knowledge, this is the first report of spontaneous regression of ATRT, with molecular heterogeneity for SMARCB1 inactivation, with no radiographic signs of recurrence at 4 years after diagnosis.

scholarly journals PDTM-15. EMBRYONIC STEM CELL SIGNATURE DRIVES ATYPICAL TERATOID/RHABDOID TUMOR DEVELOPMENT IN HUMAN PLURIPOTENT STEM CELL-DERIVED TUMOR MODEL

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi190-vi190
Author(s):  
Yoshiki Arakawa ◽  
Yukinori Terada ◽  
Yohei Mineharu ◽  
Susumu Miyamoto ◽  
Yasuhiro Yamada
Keyword(s):  
Stem Cell ◽  
Embryonic Stem Cell ◽  
Embryonic Stem ◽  
Gene Expression Signature ◽  
Rhabdoid Tumor ◽  
Human Model ◽  
Atypical Teratoid Rhabdoid Tumor ◽  
Cell Of Origin ◽  
Rhabdoid Cells ◽  
Atypical Teratoid

Abstract BACKGROUND Atypical teratoid/rhabdoid tumor (AT/RT), which harbors SMARCB1 mutation and exhibits a characteristic histology of rhabdoid cells, has a poor prognosis because of the lack of effective treatment. METHODS To investigate the pathogenesis of AT/RT, we establish human SMARCB1-deficient pluripotent stem cells (hPSCs). RESULTS Although neural progenitors have been suggested as being a cell-of-origin of AT/RT, SMARCB1-deficient hPSC-derived neural progenitor-like cells (NPLCs) give rise to mostly medulloblastoma-like tumors when transplanted into the mouse brain. In contrast, transplantation of SMARCB1-deficient hPSCs cause AT/RT-like tumor containing a large number of typical rhabdoid cells. hPSC-derived tumors exhibit activation of embryonic stem cell-like gene expression signature (ESC-like signature) compare with NPLC-derived tumors. Forced activation of ESC-like signature by expression of reprogramming factors confers rhabdoid histology in SMARCB1-deficient NPLC-derived tumors. Activation of ESC-like signature is associated with poor survival. Consistently, the activation of ESC-like signature is found in clinical specimens of AT/RT. Finally, we perform CRISPR/Cas9 knockout screening to inhibit activation of ESC-like signature in AT/RT. Our effort identifies candidate genes including RAD21 that encodes a key component within the cohesin complex. Notably, chemical inhibition of HDAC8 that indirectly targets the function of cohesin with simultaneous inhibition of EZH2 efficiently suppresses the activation of ESC-like signature and inhibits the growth of AT/RT cells both in vitro and in vivo. CONCLUSION SMARCB1-deficient hPSCs offer the first human model for AT/RT, which uncovers the unappreciated role of the activated ESC-like signature in worse prognosis and unique histology. We propose that ESC-like signature could be a crucial therapeutic target for AT/RT.

scholarly journals ATRT-30. RETROSPECTIVE ANALYSIS OF CHILDREN WITH ATYPICAL TERATOID RHABDOID TUMOR TREATED ACCORDING TO ACNS0333

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii281-iii282
Author(s):  
Lindsey Hoffman ◽  
Ashley Margol ◽  
Kelly Faulk ◽  
Sara Hutchins ◽  
Gregory Friedman ◽  
...  
Keyword(s):  
Residual Disease ◽  
Tumor Location ◽  
High Dose Chemotherapy ◽  
Rhabdoid Tumor ◽  
Published Data ◽  
High Dose ◽  
Primary Therapy ◽  
Central Nervous System Tumor ◽  
Atypical Teratoid Rhabdoid Tumor ◽  
Atypical Teratoid

Abstract Atypical teratoid rhabdoid tumor (ATRT) is a central nervous system tumor with poor outcome. ACNS0333, a Children’s Oncology Group phase 3 trial, enrolled 65 evaluable patients who received two cycles of induction chemotherapy, three cycles of consolidative high-dose chemotherapy (HDCT), and focal radiation therapy (RT) pre- or post-consolidation. Craniospinal irradiation (CSI) was left to clinician discretion. We retrospectively analyzed medical records of 27 children treated at our institutions according to ACNS0333. Median age at diagnosis was 14 months (range 4–165); 13 (48%) were male. M-stage was M0, M2, and M3 for 18 (66%), 5 (19%), and 4 (15%), respectively. Tumor location was supratentorial (n=14, 52%), infratentorial (n=12, 44%), or both (n=1, 4%). Complete resection was achieved for 17 (63%). All but one completed induction. Of 13 (51%) with residual disease at diagnosis, 5 (36%) and 7 (50%), respectively, exhibited complete and partial response to induction. Three patients progressed on therapy, and six progressed after completion of therapy at a median of 9.7 months. In all, 18 patients completed RT (16 focal/4 CSI and 6 pre-/12 post-consolidation). Three died of therapy-related toxicity (two in primary therapy and one in relapse therapy), and 8 died of disease. Sixteen patients (59%) are alive at a median follow up of 53 months (range 9–114). Of 17 with germline testing, eight (47%) had rhabdoid predisposition syndrome of whom three are alive. At the time of presentation, data for approximately 50 patients is expected, and we will compare outcomes to soon-to-be published data from ACNS0333.

Atypical Teratoid/Rhabdoid Tumor: Revisiting Histomorphology and Immunohistochemistry With Analysis of Cyclin D1 Overexpression and MYC Amplification

2020 ◽  
pp. 106689692094328
Author(s):  
Akash Pramod Sali ◽  
Sridhar Epari ◽  
T. S. Nagaraj ◽  
Ayushi Sahay ◽  
Girish Chinnaswamy ◽  
...  
Keyword(s):  
Cyclin D1 ◽  
Posterior Fossa ◽  
Negative Impact ◽  
Rhabdoid Tumor ◽  
Atypical Teratoid Rhabdoid Tumor ◽  
Posterior Fossa Tumors ◽  
Female Ratio ◽  
Rhabdoid Cells ◽  
Divergent Differentiation ◽  
Atypical Teratoid

Objectives. Atypical teratoid/rhabdoid tumor (AT/RT) is a rare malignant pediatric brain tumor, characterized by inactivation of INI1/hSNF5 gene and loss of its protein. We studied the histomorphological and immunohistochemical spectrum of this tumor including cyclin D1 expression and MYC gene amplification. Methods. Cases with INI1 loss by immunohistochemistry (IHC; from 2005 to 2018) were retrieved, reviewed, and evaluated for cyclin D1 expression by additional IHC and fluorescence in situ hybridization for MYC genes. Results. A total of 66 cases were identified. Age ranged from 1 to 20 years (≤3 years, 44 cases; >3 years, 22). Male to female ratio was 1.7:1. Tumor locations were as follows: posterior fossa: 30; supratentorial: 31; spinal: 5. AT/RT in patient ≤3 years was frequently located in the posterior fossa, composed of primitive embryonal morphology ( P = .02), rarely had ample rhabdoid cells ( P = .05), and had a negative impact on overall survival ( P = .04). The rhabdoid cells was a conspicuous component of posterior fossa tumors compared with the supratentorial ones ( P = .06). The supratentorial tumors ( P = .06), absence of rhabdoid cells ( P = .06), and the presence of immunological divergent differentiation ( P = .11) had a comparatively better outcome. Cyclin D1 overexpression (n = 46) was noted in 32 cases and was frequently seen in the posterior fossa tumors ( P = .02). CMYC (n = 42) amplification was seen in 1 case and the NMYC (n = 42) amplification in none. Conclusion. AT/RT can occur in the noninfantile age group, at nonconventional sites and frequently overexpress cyclin D1. The MYC alterations are almost nonexistent in AT/RT.

scholarly journals ATRT-03. IDENTIFICATION OF microRNA-BASED PROGNOSTIC BIOMARKERS AND CANDIDATE THERAPEUTIC AGENTS FOR ATYPICAL TERATOID/RHABDOID TUMOR

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii275-iii276
Author(s):  
Yang Zhang ◽  
Jianguo Xu
Keyword(s):  
Target Genes ◽  
Kinase Inhibitor ◽  
Therapeutic Agents ◽  
Rhabdoid Tumor ◽  
Janus Kinase ◽  
Prognostic Biomarkers ◽  
Atypical Teratoid Rhabdoid Tumor ◽  
Overlapping Genes ◽  
Hub Genes ◽  
Atypical Teratoid

Abstract BACKGROUND MicroRNA (miRNA) has been found to be involved in development of many malignant pediatric brain tumors, including atypical teratoid/rhabdoid tumor (AT/RT) that is highly aggressive and carries a dismal prognosis. The current study investigated the potential value of miRNAs and pivotal genes associated with AT/RT using bioinformatics analysis, aiming to identify new prognostic biomarkers and candidate drugs for AT/RT patients. METHODS Differentially expressed miRNAs (DEMs) and genes (DEGs) between AT/RT and normal control samples were obtained from GEO database. The target genes of DEMs were predicted via TargetScanHuman7.2 and miRDB, and then intersected with DEGs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses of overlapping genes were conducted, followed by construction of protein-protein interaction network. Hub genes were determined by Cytoscape software, and their prognostic values were evaluated using Kaplan-Meier analysis. Connectivity Map database was used to identify latent therapeutic agents. RESULTS A total of 11 DEMs (hsa-miR-1224-5p, hsa-miR-128-3p, hsa-miR-17-5p, hsa-miR-18b-5p, hsa-miR-29c-5p, hsa-miR-329-3p, hsa-miR-379-5p, hsa-miR-433-3p, hsa-miR-488-5p, hsa-miR-656-3p and hsa-miR-885-5p) were screened. By intersecting 3275 predicted target genes and 925 DEGs, we finally identified 226 overlapping genes that were enriched in pathways in cancer and MAPK signaling pathway. Four hub genes (GRIA2, NRXN1, SLC6A1 and SYT1) were significantly associated with the overall survival of AT/RT patients. Candidate drugs included histone deacetylase inhibitor (givinostat), DNA synthesis inhibitor (floxuridine), cyclin-dependent kinase inhibitor (purvalanol) and janus kinase inhibitor (lestaurtinib). CONCLUSION In summary, this study systematically analyzed AT/RT-related miRNAs and pivotal genes to provide novel prognostic biomarkers and potential therapeutic agents.

Atypical Teratoid Rhabdoid Tumor in a Newborn: Can IVF Be a Risk Factor?

2021 ◽  
pp. 1-5
Author(s):  
Turkay Rzayev ◽  
Kubra Gokce ◽  
Safak Gucyetmez ◽  
Suheyla Bozkurt ◽  
Adnan Dagcinar ◽  
...  
Keyword(s):  
Risk Factor ◽  
Rhabdoid Tumor ◽  
Atypical Teratoid Rhabdoid Tumor ◽  
Atypical Teratoid

Epithelioid Sarcoma Arising in a Long-Term Survivor of an Atypical Teratoid/Rhabdoid Tumor in a Patient With Rhabdoid Tumor Predisposition Syndrome

2021 ◽  
pp. 109352662098649
Author(s):  
Tiffany G Baker ◽  
Michael J Lyons ◽  
Lee Leddy ◽  
David M Parham ◽  
Cynthia T Welsh
Keyword(s):  
Epithelioid Sarcoma ◽  
Rhabdoid Tumor ◽  
Malignant Rhabdoid Tumor ◽  
Atypical Teratoid Rhabdoid Tumor ◽  
Diagnostic Challenge ◽  
Patient Demographics ◽  
Immunohistochemical Markers ◽  
Genetic Aberration ◽  
Atypical Teratoid ◽  
Rhabdoid Tumors

Rhabdoid tumor predisposition syndrome (RTPS) is defined as the presence of a SMARCB1 or SMARCA4 genetic aberration in a patient with malignant rhabdoid tumor. Patients with RTPS are more likely to present with synchronous or metachronous rhabdoid tumors. Based on the current state of rhabdoid tumor taxonomy, these diagnoses are based largely on patient demographics, anatomic location of disease, and immunohistochemistry, despite their nearly identical histologic and immunohistochemical profiles. Thus, the true distinction between such tumors remains a diagnostic challenge. Central nervous system atypical teratoid/rhabdoid tumor (AT/RT) is a rare, aggressive, primarily pediatric malignancy with variable histologic features and a well documented association with loss of SMARCB1 expression. Epithelioid sarcoma (ES) is a rare soft tissue tumor arising in patients of all ages and characteristically staining for both mesenchymal and epithelial immunohistochemical markers while usually demonstrating loss of SMARCB1 expression. To our knowledge we herein present the first documented case of a patient with RTPS who presented with metachronous AT/RT and ES.

scholarly journals ATRT-04. INHERITED RHABDOID PREDISPOSITION SYNDROME: A CASE OF CHOROID PLEXUS CARCINOMA AND ATYPICAL TERATOID RHABDOID TUMOR IN SIBLINGS

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii276-iii276
Author(s):  
Alexis Judd ◽  
Erin Wright ◽  
Sarah Rush
Keyword(s):  
Overall Survival ◽  
Choroid Plexus ◽  
Disease Recurrence ◽  
Genetic Alterations ◽  
Rhabdoid Tumor ◽  
Choroid Plexus Carcinoma ◽  
High Dose ◽  
Atypical Teratoid Rhabdoid Tumor ◽  
Increased Risk ◽  
Atypical Teratoid

Abstract Choroid plexus carcinoma (CPC) and Atypical teratoid/rhabdoid tumor (ATRT) are aggressive, malignant brain cancers most commonly arising in children less than 3 years of age. These tumors often have genetic alterations in the tumor suppressor gene SMARCB1/INI1. Rhabdoid predisposition syndrome (RTPS) categorizes patients with germline mutations in SMARCB1 or SMARCA4, leading to a markedly increased risk of developing rhabdoid tumors. Both CPC and ATRT have been demonstrated in patients with these rhabdoid predisposition syndromes. In general, these tumors tend to have a poor prognosis. However, with the presence of a SMARCB1 mutation they may have improved overall survival. We present two interesting cases of siblings with maternally inherited SMARCB1 mutations: one a 21-month-old male who presented with an ATRT and another a 10 month old female who presented with a CPC. The ATRT was treated as per the Children’s Oncology Group study ACNS0333 with high dose chemotherapy and stem cell rescue as well as cranial radiation. The CPC was treated as per CPT-SIOP 2009 with etoposide, cyclophosphamide and vincristine. Unlike other patients with these aggressive tumors, both of these patients are alive without evidence of disease recurrence 8 and 7 years post therapy, respectively. Additional genomic testing on both tumors is currently pending in order to potentially identify other mutations that may impact survival. These cases further illustrate the similar profile of two very different tumors with improved overall survival that may be secondary to mutations in SMARCB1 in RTPS.

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