Atypical teratoid/rhabdoid tumor (AT/RT) is a highly aggressive embryonal central nervous system tumor that predominantly affects infants and young children. AT/RT is defined by SMARCB1 loss and, rarely, SMARCA4 loss within the SWI/SNF chromatin-remodeling complex. Consistent with dismech cancer curation guidance, this entry treats AT/RT as the disease-level mechanism graph and models TYR, SHH, and MYC as flat molecular subgroup facets rather than separate disorder pages.
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name: Atypical Teratoid/Rhabdoid Tumor
creation_date: '2026-04-12T20:00:00Z'
updated_date: '2026-05-08T16:21:17Z'
description: >-
Atypical teratoid/rhabdoid tumor (AT/RT) is a highly aggressive embryonal
central nervous system tumor that predominantly affects infants and young
children. AT/RT is defined by SMARCB1 loss and, rarely, SMARCA4 loss within
the SWI/SNF chromatin-remodeling complex. Consistent with dismech cancer
curation guidance, this entry treats AT/RT as the disease-level mechanism
graph and models TYR, SHH, and MYC as flat molecular subgroup facets rather
than separate disorder pages.
categories:
- Central Nervous System Neoplasm
- Pediatric Brain Tumor
- Embryonal Tumor
- Molecularly Defined Tumor
- SWI/SNF-Deficient Tumor
parents:
- rhabdoid tumor
disease_term:
preferred_term: atypical teratoid rhabdoid tumor
term:
id: MONDO:0020560
label: atypical teratoid rhabdoid tumor
epidemiology:
- name: Infant-predominant pediatric brain tumor
description: >-
AT/RT is rare among pediatric brain tumors overall but disproportionately
represented in infants and children younger than 3 years of age.
evidence:
- reference: PMID:22988546
reference_title: "Atypical teratoid rhabdoid tumor: current therapy and future directions."
supports: SUPPORT
evidence_source: OTHER
snippet: "Atypical teratoid rhabdoid tumors (ATRTs) are rare central nervous system tumors that comprise approximately 1-2% of all pediatric brain tumors; however, in patients less than 3 years of age this tumor accounts for up to 20% of cases."
explanation: >-
This review provides the standard disease-level epidemiology framing used
clinically for AT/RT, highlighting its enrichment in infants and very
young children.
has_subtypes:
- name: TYR
display_name: AT/RT-TYR
classification: molecular
description: >-
Consensus methylation-defined molecular subgroup of AT/RT. It is retained as
a flat subtype facet within the AT/RT disease graph rather than as a separate
dismech disease page.
evidence:
- reference: PMID:41374972
reference_title: "Atypical Teratoid Rhabdoid Tumor: How Tumor Diagnostic Methods in the Laboratory Have Evolved over the Past 40 Years."
supports: SUPPORT
evidence_source: OTHER
snippet: "The integration of immunohistochemical markers with advanced molecular diagnostics-including next-generation sequencing, DNA methylation profiling, and gene enrichment analyses-has facilitated robust tumor classification and the identification of three molecular subgroups: TYR, SHH, and MYC."
explanation: >-
This review explicitly names TYR as one of the three consensus molecular
subgroups used to facet AT/RT without implying a separate disease page.
- name: SHH
display_name: AT/RT-SHH
classification: molecular
description: >-
Consensus methylation-defined molecular subgroup of AT/RT. It is modeled as
a molecular subgroup axis inside the AT/RT page.
evidence:
- reference: PMID:41374972
reference_title: "Atypical Teratoid Rhabdoid Tumor: How Tumor Diagnostic Methods in the Laboratory Have Evolved over the Past 40 Years."
supports: SUPPORT
evidence_source: OTHER
snippet: "The integration of immunohistochemical markers with advanced molecular diagnostics-including next-generation sequencing, DNA methylation profiling, and gene enrichment analyses-has facilitated robust tumor classification and the identification of three molecular subgroups: TYR, SHH, and MYC."
explanation: >-
This review explicitly names SHH as one of the three consensus molecular
subgroups used to facet AT/RT.
- name: MYC
display_name: AT/RT-MYC
classification: molecular
description: >-
Consensus methylation-defined molecular subgroup of AT/RT. It is modeled as
a molecular subgroup facet within the single AT/RT disease entry.
evidence:
- reference: PMID:41374972
reference_title: "Atypical Teratoid Rhabdoid Tumor: How Tumor Diagnostic Methods in the Laboratory Have Evolved over the Past 40 Years."
supports: SUPPORT
evidence_source: OTHER
snippet: "The integration of immunohistochemical markers with advanced molecular diagnostics-including next-generation sequencing, DNA methylation profiling, and gene enrichment analyses-has facilitated robust tumor classification and the identification of three molecular subgroups: TYR, SHH, and MYC."
explanation: >-
This review explicitly names MYC as one of the three consensus molecular
subgroups used to facet AT/RT.
pathophysiology:
- name: SMARCB1 or SMARCA4 Inactivation
description: >-
AT/RT is defined by inactivation of the SWI/SNF core subunits SMARCB1 and,
more rarely, SMARCA4. This is the shared disease-defining lesion across the
AT/RT molecular subgroups.
genes:
- preferred_term: SMARCB1
term:
id: hgnc:11103
label: SMARCB1
- preferred_term: SMARCA4
term:
id: hgnc:11100
label: SMARCA4
protein_complexes:
- preferred_term: SWI/SNF complex
term:
id: GO:0016514
label: SWI/SNF complex
evidence:
- reference: PMID:41374972
reference_title: "Atypical Teratoid Rhabdoid Tumor: How Tumor Diagnostic Methods in the Laboratory Have Evolved over the Past 40 Years."
supports: SUPPORT
evidence_source: OTHER
snippet: "AT/RT now encompasses CNS tumors characterized by SMARCB1 (INI-1) or SMARCA4 (BRG-1) alterations within the SWI/SNF chromatin-remodeling complex."
explanation: >-
This review directly defines AT/RT by SMARCB1 or SMARCA4 alterations in
the SWI/SNF complex, supporting the disease-defining initiating lesion.
downstream:
- target: SWI/SNF Chromatin Remodeling Defect
description: Core subunit loss disables normal SWI/SNF chromatin remodeling
- name: SWI/SNF Chromatin Remodeling Defect
description: >-
Loss of SMARCB1 or SMARCA4 impairs the SWI/SNF chromatin-remodeling machinery,
shifting AT/RT biology toward an epigenetically driven tumor state.
biological_processes:
- preferred_term: chromatin remodeling
modifier: ABNORMAL
term:
id: GO:0006338
label: chromatin remodeling
evidence:
- reference: PMID:37020038
reference_title: "Atypical teratoid/rhabdoid tumoroids reveal subgroup-specific drug vulnerabilities."
supports: SUPPORT
evidence_source: IN_VITRO
snippet: "They are genetically defined by alterations in the SWI/SNF chromatin remodeling complex members SMARCB1 or SMARCA4."
explanation: >-
This AT/RT tumoroid study directly links the defining genomic lesion to
SWI/SNF chromatin-remodeling complex disruption.
downstream:
- target: Subtype-Specific Enhancer Dysregulation
description: Epigenetic dysregulation segregates into distinct subgroup programs
- name: Subtype-Specific Enhancer Dysregulation
description: >-
Despite a simple recurrent genetic landscape, AT/RT segregates into distinct
epigenetic subgroups with different enhancer states and regulatory networks.
biological_processes:
- preferred_term: regulation of gene expression
modifier: ABNORMAL
term:
id: GO:0010468
label: regulation of gene expression
evidence:
- reference: PMID:26923874
reference_title: "Atypical Teratoid/Rhabdoid Tumors Are Comprised of Three Epigenetic Subgroups with Distinct Enhancer Landscapes."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Three distinct molecular subgroups of ATRTs, associated with differences in demographics, tumor location, and type of SMARCB1 alterations, were identified."
explanation: >-
This methylation and integrated molecular profiling study identifies the
three consensus molecular subgroups within AT/RT.
- reference: PMID:26923874
reference_title: "Atypical Teratoid/Rhabdoid Tumors Are Comprised of Three Epigenetic Subgroups with Distinct Enhancer Landscapes."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Whole-genome bisulfite sequencing and H3K27Ac chromatin-immunoprecipitation sequencing of primary tumors, however, revealed clear differences, leading to the identification of subgroup-specific regulatory networks and potential therapeutic targets."
explanation: >-
This provides direct human-tumor evidence that subgroup biology is driven
by enhancer and regulatory-network differences rather than additional
recurrent coding mutations.
- reference: PMID:37020038
reference_title: "Atypical teratoid/rhabdoid tumoroids reveal subgroup-specific drug vulnerabilities."
supports: SUPPORT
evidence_source: IN_VITRO
snippet: "We demonstrate that ATRT tumoroids retain subgroup-specific epigenetic and gene expression profiles."
explanation: >-
In vitro AT/RT tumoroids recapitulate subgroup-specific epigenetic and
transcriptional programs, reinforcing the atomic subgroup-program node.
downstream:
- target: Aggressive Tumor Cell Proliferation
description: Epigenetic dysregulation sustains rapid malignant growth
- name: Aggressive Tumor Cell Proliferation
description: >-
AT/RT typically displays rapid progression, short time to recurrence, and
highly aggressive growth behavior.
biological_processes:
- preferred_term: cell population proliferation
modifier: INCREASED
term:
id: GO:0008283
label: cell population proliferation
evidence:
- reference: PMID:16048294
reference_title: "Atypical teratoid/rhabdoid tumors of the central nervous system: management and outcomes."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "They commonly present in childhood, and have a rapidly progressive clinical course with a survival time of less than 1 year."
explanation: >-
This cohort abstract supports the clinically aggressive, rapidly
progressive proliferative behavior characteristic of AT/RT.
histopathology:
- name: Composite Rhabdoid-Embryonal Histology
finding_term:
preferred_term: atypical teratoid/rhabdoid tumor
term:
id: NCIT:C6906
label: Atypical Teratoid/Rhabdoid Tumor
diagnostic: true
description: >-
AT/RT is a polymorphous embryonal tumor with rhabdoid, primitive
neuroectodermal, epithelial, and mesenchymal components rather than a
uniform small-round-blue-cell morphology.
evidence:
- reference: PMID:10437379
reference_title: "Clinicopathological characteristics of atypical teratoid/rhabdoid tumor."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Histologically, atypical teratoid/rhabdoid tumor is defined as a polymorphous neoplasm often featuring rhabdoid, PNET, epithelial, and mesenchymal components."
explanation: >-
This pathology series provides the disease-defining microscopic composite
morphology used for histopathologic grounding.
phenotypes:
- category: Neurological
name: Vomiting
description: >-
Vomiting is a common presenting feature, usually reflecting intracranial
mass effect and increased intracranial pressure.
phenotype_term:
preferred_term: Vomiting
term:
id: HP:0002013
label: Vomiting
evidence:
- reference: PMID:16048294
reference_title: "Atypical teratoid/rhabdoid tumors of the central nervous system: management and outcomes."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Signs and symptoms began, on average, a little more than 1 month before diagnosis and included the following: headache (36%), nausea and vomiting (46%), lethargy (18%), seizures (27%), cranial nerve findings (46%), ataxia (18%), long tract findings (18%), and hydrocephalus (46%)."
explanation: This cohort abstract directly reports nausea and vomiting among common presenting symptoms of AT/RT.
- category: Neurological
name: Headache
description: >-
Headache is a frequent presenting symptom caused by the intracranial tumor
burden and associated pressure effects.
phenotype_term:
preferred_term: Headache
term:
id: HP:0002315
label: Headache
evidence:
- reference: PMID:16048294
reference_title: "Atypical teratoid/rhabdoid tumors of the central nervous system: management and outcomes."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Signs and symptoms began, on average, a little more than 1 month before diagnosis and included the following: headache (36%), nausea and vomiting (46%), lethargy (18%), seizures (27%), cranial nerve findings (46%), ataxia (18%), long tract findings (18%), and hydrocephalus (46%)."
explanation: This cohort abstract directly reports headache as a common presenting symptom of AT/RT.
- category: Neurological
name: Ataxia
description: >-
Ataxia is a common presenting sign, especially for posterior fossa tumors.
phenotype_term:
preferred_term: Ataxia
term:
id: HP:0001251
label: Ataxia
evidence:
- reference: PMID:16048294
reference_title: "Atypical teratoid/rhabdoid tumors of the central nervous system: management and outcomes."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Signs and symptoms began, on average, a little more than 1 month before diagnosis and included the following: headache (36%), nausea and vomiting (46%), lethargy (18%), seizures (27%), cranial nerve findings (46%), ataxia (18%), long tract findings (18%), and hydrocephalus (46%)."
explanation: This cohort abstract directly reports ataxia among the presenting neurologic manifestations of AT/RT.
- category: Neurological
name: Hydrocephalus
description: >-
Hydrocephalus is a common presenting complication caused by tumor-related
cerebrospinal fluid obstruction.
phenotype_term:
preferred_term: Hydrocephalus
term:
id: HP:0000238
label: Hydrocephalus
evidence:
- reference: PMID:16048294
reference_title: "Atypical teratoid/rhabdoid tumors of the central nervous system: management and outcomes."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Signs and symptoms began, on average, a little more than 1 month before diagnosis and included the following: headache (36%), nausea and vomiting (46%), lethargy (18%), seizures (27%), cranial nerve findings (46%), ataxia (18%), long tract findings (18%), and hydrocephalus (46%)."
explanation: This cohort abstract directly reports hydrocephalus as a common presenting feature of AT/RT.
biochemical:
- name: INI1 (SMARCB1/BAF47) Immunohistochemistry
notes: >-
Loss of nuclear INI1 staining is the canonical diagnostic biomarker for most
AT/RTs and reflects SMARCB1 inactivation.
evidence:
- reference: PMID:26769252
reference_title: "Atypical Teratoid/Rhabdoid Tumor (AT/RT) Arising From Ependymoma: A Type of AT/RT Secondarily Developing From Other Primary Central Nervous System Tumors."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Atypical teratoid/rhabdoid tumors (AT/RT) are rare, aggressive, embryonal brain tumors that occur most frequently in very young children; they are characterized by rhabdoid cells and loss of INI1 protein nuclear expression."
explanation: >-
This pathology report explicitly identifies loss of INI1 nuclear expression
as a defining diagnostic feature of AT/RT.
- name: BRG1 (SMARCA4) Immunohistochemistry
notes: >-
Loss of BRG1 supports the rare SMARCA4-deficient AT/RT subset when INI1 is
retained.
evidence:
- reference: PMID:41374972
reference_title: "Atypical Teratoid Rhabdoid Tumor: How Tumor Diagnostic Methods in the Laboratory Have Evolved over the Past 40 Years."
supports: SUPPORT
evidence_source: OTHER
snippet: "AT/RT now encompasses CNS tumors characterized by SMARCB1 (INI-1) or SMARCA4 (BRG-1) alterations within the SWI/SNF chromatin-remodeling complex."
explanation: >-
This review supports inclusion of BRG1/SMARCA4 loss as the rare alternate
diagnostic branch within the AT/RT disease spectrum.
genetic:
- name: SMARCB1
gene_term:
preferred_term: SMARCB1
term:
id: hgnc:11103
label: SMARCB1
association: Somatic/Germline Loss-of-Function
notes: >-
SMARCB1 is the dominant disease-defining driver gene in AT/RT. Both somatic
and germline loss occur, and germline events overlap with rhabdoid tumor
predisposition syndrome.
evidence:
- reference: PMID:41374972
reference_title: "Atypical Teratoid Rhabdoid Tumor: How Tumor Diagnostic Methods in the Laboratory Have Evolved over the Past 40 Years."
supports: SUPPORT
evidence_source: OTHER
snippet: "AT/RT now encompasses CNS tumors characterized by SMARCB1 (INI-1) or SMARCA4 (BRG-1) alterations within the SWI/SNF chromatin-remodeling complex."
explanation: >-
This review directly places SMARCB1 alteration at the center of AT/RT
disease definition.
- name: SMARCA4
gene_term:
preferred_term: SMARCA4
term:
id: hgnc:11100
label: SMARCA4
association: Rare Somatic/Germline Loss-of-Function
notes: >-
SMARCA4 alteration is a rare alternative driver in INI1-retained AT/RT and
should be considered when the histology is compatible but SMARCB1 protein
expression is preserved.
evidence:
- reference: PMID:41374972
reference_title: "Atypical Teratoid Rhabdoid Tumor: How Tumor Diagnostic Methods in the Laboratory Have Evolved over the Past 40 Years."
supports: SUPPORT
evidence_source: OTHER
snippet: "AT/RT now encompasses CNS tumors characterized by SMARCB1 (INI-1) or SMARCA4 (BRG-1) alterations within the SWI/SNF chromatin-remodeling complex."
explanation: >-
This review directly supports rare SMARCA4-altered AT/RT as part of the
disease spectrum.
treatments:
- name: Maximal Safe Surgical Resection
description: >-
Surgery is used for diagnosis, decompression, and maximal cytoreduction
before adjuvant therapy.
treatment_term:
preferred_term: surgical resection
term:
id: MAXO:0000004
label: surgical procedure
evidence:
- reference: PMID:25646852
reference_title: "Intracranial atypical teratoid rhabdoid tumor: current management and a single institute experience of 15 patients from north India."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Maximal safe resection followed by craniospinal irradiation and systemic chemotherapy with ICE or VAC regimen is a reasonable treatment strategy in this uncommon malignancy."
explanation: >-
This clinical series supports maximal safe resection as the surgical
backbone of multimodality AT/RT treatment.
- name: Intensive Multiagent Chemotherapy
description: >-
Multiagent chemotherapy, often including high-dose chemotherapy with stem
cell rescue, is a core component of contemporary AT/RT treatment protocols.
treatment_term:
preferred_term: chemotherapy
term:
id: MAXO:0000647
label: chemotherapy
evidence:
- reference: PMID:32105509
reference_title: "Efficacy of High-Dose Chemotherapy and Three-Dimensional Conformal Radiation for Atypical Teratoid/Rhabdoid Tumor: A Report From the Children's Oncology Group Trial ACNS0333."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "After surgery, they received 2 courses of multiagent chemotherapy, followed by 3 courses of high-dose chemotherapy with peripheral blood stem cell rescue and involved-field radiation therapy."
explanation: >-
ACNS0333 directly documents a modern intensive chemotherapy backbone that
includes high-dose chemotherapy with stem cell rescue.
- reference: PMID:33138347
reference_title: "Atypical Teratoid/Rhabdoid Tumor of the Central Nervous System in Children under the Age of 3 Years."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Aggressive therapy including early adjuvant radiotherapy and HDCT could be considered to improve outcomes of ATRT in children under the age of 3 years."
explanation: >-
This multicenter infant cohort supports high-dose chemotherapy as part of
aggressive therapy associated with improved outcomes in young children.
- name: Adjuvant Radiation Therapy
description: >-
Focal or craniospinal radiation is used for local and neuraxis control and
remains an important component of modern AT/RT therapy despite age-related
toxicity concerns in infants.
treatment_term:
preferred_term: radiation therapy
term:
id: MAXO:0000014
label: radiation therapy
evidence:
- reference: PMID:32105509
reference_title: "Efficacy of High-Dose Chemotherapy and Three-Dimensional Conformal Radiation for Atypical Teratoid/Rhabdoid Tumor: A Report From the Children's Oncology Group Trial ACNS0333."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "The ACNS0333 regimen dramatically improved survival compared with historical therapies for patients with AT/RT."
explanation: >-
ACNS0333 used involved-field radiation as part of the regimen that improved
survival relative to historical therapy.
- reference: PMID:33138347
reference_title: "Atypical Teratoid/Rhabdoid Tumor of the Central Nervous System in Children under the Age of 3 Years."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Aggressive therapy including early adjuvant radiotherapy and HDCT could be considered to improve outcomes of ATRT in children under the age of 3 years."
explanation: >-
This multicenter infant cohort directly supports early adjuvant
radiotherapy as an outcome-improving component of aggressive therapy.
references:
- reference: DOI:10.1002/gcc.23195
title: 'Constitutional balanced translocations involving <scp><i>SMARCB1</i></scp>: A rare cause of rhabdoid tumor predisposition syndrome'
found_in:
- Atypical_Teratoid_Rhabdoid_Tumor-deep-research-falcon.md
findings:
- statement: Rhabdoid Tumor Predisposition Syndrome 1 (RTPS1) confers an increased risk of developing rhabdoid tumors and is caused by germline mutations in SMARCB1.
supporting_text: Rhabdoid Tumor Predisposition Syndrome 1 (RTPS1) confers an increased risk of developing rhabdoid tumors and is caused by germline mutations in SMARCB1.
evidence:
- reference: DOI:10.1002/gcc.23195
reference_title: 'Constitutional balanced translocations involving <scp><i>SMARCB1</i></scp>: A rare cause of rhabdoid tumor predisposition syndrome'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Rhabdoid Tumor Predisposition Syndrome 1 (RTPS1) confers an increased risk of developing rhabdoid tumors and is caused by germline mutations in SMARCB1.
explanation: Deep research cited this publication as relevant literature for Atypical Teratoid Rhabdoid Tumor.
- reference: DOI:10.1007/s00401-020-02250-7
title: Atypical teratoid/rhabdoid tumors (ATRTs) with SMARCA4 mutation are molecularly distinct from SMARCB1-deficient cases
found_in:
- Atypical_Teratoid_Rhabdoid_Tumor-deep-research-falcon.md
findings:
- statement: Atypical teratoid/rhabdoid tumors (ATRTs) are very aggressive childhood malignancies of the central nervous system.
supporting_text: Atypical teratoid/rhabdoid tumors (ATRTs) are very aggressive childhood malignancies of the central nervous system.
evidence:
- reference: DOI:10.1007/s00401-020-02250-7
reference_title: Atypical teratoid/rhabdoid tumors (ATRTs) with SMARCA4 mutation are molecularly distinct from SMARCB1-deficient cases
supports: SUPPORT
evidence_source: OTHER
snippet: Atypical teratoid/rhabdoid tumors (ATRTs) are very aggressive childhood malignancies of the central nervous system.
explanation: Deep research cited this publication as relevant literature for Atypical Teratoid Rhabdoid Tumor.
- reference: DOI:10.1007/s00401-023-02608-7
title: Recurrent atypical teratoid/rhabdoid tumors (AT/RT) reveal discrete features of progression on histology, epigenetics, copy number profiling, and transcriptomics
found_in:
- Atypical_Teratoid_Rhabdoid_Tumor-deep-research-falcon.md
findings:
- statement: Atypical teratoid/rhabdoid tumors (AT/RT) are the most common malignant brain tumors manifesting in infancy.
supporting_text: Atypical teratoid/rhabdoid tumors (AT/RT) are the most common malignant brain tumors manifesting in infancy.
evidence:
- reference: DOI:10.1007/s00401-023-02608-7
reference_title: Recurrent atypical teratoid/rhabdoid tumors (AT/RT) reveal discrete features of progression on histology, epigenetics, copy number profiling, and transcriptomics
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Atypical teratoid/rhabdoid tumors (AT/RT) are the most common malignant brain tumors manifesting in infancy.
explanation: Deep research cited this publication as relevant literature for Atypical Teratoid Rhabdoid Tumor.
- reference: DOI:10.1093/neuonc/noaa046
title: Advancing biology-based therapeutic approaches for atypical teratoid rhabdoid tumors
found_in:
- Atypical_Teratoid_Rhabdoid_Tumor-deep-research-falcon.md
findings:
- statement: 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.
supporting_text: 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.
evidence:
- reference: DOI:10.1093/neuonc/noaa046
reference_title: Advancing biology-based therapeutic approaches for atypical teratoid rhabdoid tumors
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: 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.
explanation: Deep research cited this publication as relevant literature for Atypical Teratoid Rhabdoid Tumor.
- reference: DOI:10.1093/noajnl/vdae158
title: Approaches for prevention of tumors in patients with rhabdoid tumor predisposition syndrome
found_in:
- Atypical_Teratoid_Rhabdoid_Tumor-deep-research-falcon.md
findings:
- statement: Patients with rhabdoid tumor predisposition syndrome (RTPS) harbor germline alterations in the epigenetic regulator genes SMARCB1 or SMARCA4.
supporting_text: Patients with rhabdoid tumor predisposition syndrome (RTPS) harbor germline alterations in the epigenetic regulator genes SMARCB1 or SMARCA4.
evidence:
- reference: DOI:10.1093/noajnl/vdae158
reference_title: Approaches for prevention of tumors in patients with rhabdoid tumor predisposition syndrome
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Patients with rhabdoid tumor predisposition syndrome (RTPS) harbor germline alterations in the epigenetic regulator genes SMARCB1 or SMARCA4.
explanation: Deep research cited this publication as relevant literature for Atypical Teratoid Rhabdoid Tumor.
- reference: DOI:10.1093/noajnl/vdae162
title: Development and epigenetic regulation of Atypical teratoid/rhabdoid tumors in the context of cell-of-origin and halted cell differentiation
found_in:
- Atypical_Teratoid_Rhabdoid_Tumor-deep-research-falcon.md
findings:
- statement: Atypical teratoid/rhabdoid tumors (AT/RTs) are aggressive brain tumors primarily observed in infants.
supporting_text: Atypical teratoid/rhabdoid tumors (AT/RTs) are aggressive brain tumors primarily observed in infants.
evidence:
- reference: DOI:10.1093/noajnl/vdae162
reference_title: Development and epigenetic regulation of Atypical teratoid/rhabdoid tumors in the context of cell-of-origin and halted cell differentiation
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Atypical teratoid/rhabdoid tumors (AT/RTs) are aggressive brain tumors primarily observed in infants.
explanation: Deep research cited this publication as relevant literature for Atypical Teratoid Rhabdoid Tumor.
- reference: DOI:10.1093/nop/npad005
title: Current advances in immunotherapy for atypical teratoid rhabdoid tumor (ATRT)
found_in:
- Atypical_Teratoid_Rhabdoid_Tumor-deep-research-falcon.md
findings:
- statement: 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.
supporting_text: 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.
evidence:
- reference: DOI:10.1093/nop/npad005
reference_title: Current advances in immunotherapy for atypical teratoid rhabdoid tumor (ATRT)
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: 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.
explanation: Deep research cited this publication as relevant literature for Atypical Teratoid Rhabdoid Tumor.
- reference: DOI:10.26508/lsa.202302088
title: Aberrant DNA methylation distorts developmental trajectories in atypical teratoid/rhabdoid tumors
found_in:
- Atypical_Teratoid_Rhabdoid_Tumor-deep-research-falcon.md
findings:
- statement: Atypical teratoid/rhabdoid tumors (AT/RTs) are pediatric brain tumors known for their aggressiveness and aberrant but still unresolved epigenetic regulation.
supporting_text: Atypical teratoid/rhabdoid tumors (AT/RTs) are pediatric brain tumors known for their aggressiveness and aberrant but still unresolved epigenetic regulation.
evidence:
- reference: DOI:10.26508/lsa.202302088
reference_title: Aberrant DNA methylation distorts developmental trajectories in atypical teratoid/rhabdoid tumors
supports: SUPPORT
evidence_source: OTHER
snippet: Atypical teratoid/rhabdoid tumors (AT/RTs) are pediatric brain tumors known for their aggressiveness and aberrant but still unresolved epigenetic regulation.
explanation: Deep research cited this publication as relevant literature for Atypical Teratoid Rhabdoid Tumor.
- reference: DOI:10.3390/cancers18010008
title: 'Histogenesis of Atypical Teratoid Rhabdoid Tumors: Anatomical and Embryological Perspectives'
found_in:
- Atypical_Teratoid_Rhabdoid_Tumor-deep-research-falcon.md
findings:
- statement: Atypical teratoid/rhabdoid tumors (ATRTs) are rare, malignant central nervous system (CNS) neoplasms that predominantly affect infants and young children.
supporting_text: Atypical teratoid/rhabdoid tumors (ATRTs) are rare, malignant central nervous system (CNS) neoplasms that predominantly affect infants and young children.
evidence:
- reference: DOI:10.3390/cancers18010008
reference_title: 'Histogenesis of Atypical Teratoid Rhabdoid Tumors: Anatomical and Embryological Perspectives'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Atypical teratoid/rhabdoid tumors (ATRTs) are rare, malignant central nervous system (CNS) neoplasms that predominantly affect infants and young children.
explanation: Deep research cited this publication as relevant literature for Atypical Teratoid Rhabdoid Tumor.
- reference: DOI:10.3390/jmp6020013
title: The Current Landscape of Molecular Pathology for the Diagnosis and Treatment of Atypical Teratoid Rhabdoid Tumor
found_in:
- Atypical_Teratoid_Rhabdoid_Tumor-deep-research-falcon.md
findings:
- statement: Atypical teratoid rhabdoid tumor (ATRT) is a rare, aggressive pediatric central nervous system (CNS) tumor that predominantly affects children under the age of 3.
supporting_text: Atypical teratoid rhabdoid tumor (ATRT) is a rare, aggressive pediatric central nervous system (CNS) tumor that predominantly affects children under the age of 3.
evidence:
- reference: DOI:10.3390/jmp6020013
reference_title: The Current Landscape of Molecular Pathology for the Diagnosis and Treatment of Atypical Teratoid Rhabdoid Tumor
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Atypical teratoid rhabdoid tumor (ATRT) is a rare, aggressive pediatric central nervous system (CNS) tumor that predominantly affects children under the age of 3.
explanation: Deep research cited this publication as relevant literature for Atypical Teratoid Rhabdoid Tumor.
ATRT is a rare, highly aggressive embryonal tumor of the CNS that predominantly affects infants and very young children. A 2023 review summarizes: “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.” (Tran 2023-01, Neuro-Oncology Practice; https://doi.org/10.1093/nop/npad005) (tran2023currentadvancesin pages 1-2).
ATRT is now understood as a molecularly defined, epigenetically driven tumor entity with marked subgroup heterogeneity despite relatively low recurrent mutational burden beyond SWI/SNF genes (SMARCB1/SMARCA4). The tumor is genetically “defined by alterations in the SWI/SNF chromatin remodeling complex members SMARCB1 or SMARCA4” (Paassen 2023-04, Oncogene; https://doi.org/10.1038/s41388-023-02681-y) (reddy2020efficacyofhighdose pages 1-2).
Most information here is aggregated from cooperative-group clinical trials, multicenter molecular cohorts, and contemporary reviews (reddy2020efficacyofhighdose pages 1-2, tran2023currentadvancesin pages 1-2, holdhof2021atypicalteratoidrhabdoidtumors pages 1-2). Case reports exist but are not the basis for the core disease definition in this report.
Core genetic cause: biallelic inactivation of SWI/SNF chromatin-remodeling genes. - SMARCB1 loss is the dominant lesion; SMARCA4 loss is rare. A 2021 Acta Neuropathologica study states: “The underlying genetic cause are inactivating bi-allelic mutations in SMARCB1 or (rarely) in SMARCA4.” (Holdhof 2021-12; https://doi.org/10.1007/s00401-020-02250-7) (holdhof2021atypicalteratoidrhabdoidtumors pages 1-2). - A 2024 review reiterates: “The only characteristic, recurrent genetic aberration of AT/RTs is biallelic inactivation of SMARCB1 (or SMARCA4).” (Huhtala 2024-09, Neuro-Oncology Advances; https://doi.org/10.1093/noajnl/vdae162) (huhtala2024developmentandepigenetic pages 1-2).
Epigenetic dysregulation as an etiologic driver: ATRT biology is dominated by epigenetic and chromatin consequences of SWI/SNF disruption. In ATRT, “aberrant DNA methylation–driven epigenetic regulation…maintains the malignant, low differentiation cell state” (Pekkarinen 2024-03, Life Science Alliance; https://doi.org/10.26508/lsa.202302088) (huhtala2024developmentandepigenetic pages 1-2).
No protective factors or gene–environment interactions were identified in the retrieved evidence set; ATRT is predominantly driven by genetic/epigenetic mechanisms (huhtala2024developmentandepigenetic pages 1-2, holdhof2021atypicalteratoidrhabdoidtumors pages 1-2).
ATRT presentation reflects rapid tumor growth, mass effect, and location-dependent neurologic deficits. A 2020 cooperative-group trial paper describes ATRT as “an aggressive, early-childhood brain tumor” (Reddy 2020-04, J Clin Oncol; https://doi.org/10.1200/JCO.19.01776) (reddy2020efficacyofhighdose pages 1-2).
The 2026 case series (not required by the user’s priority years but consistent with core phenotype) describes intracranial hypertension and seizures in lateral-ventricle ATRT (not cited here because not extracted as evidence in this run).
The following HPO mappings are suggested based on typical CNS tumor presentation; precise frequency-by-term was not available in the retrieved evidence: - HP:0001298 Encephalopathy / impaired consciousness (mass effect) - HP:0002315 Headache - HP:0002013 Vomiting - HP:0001250 Seizures - HP:0001263 Developmental regression (common in infant brain tumors) - HP:0001270 Motor delay / weakness - HP:0000252 Microcephaly (treatment-related; not extracted here)
(These HPO codes are suggested for structuring and should be validated against clinical series for ATRT-specific frequencies; no citable evidence in this run provides per-HPO frequencies.)
Commonly involve loss-of-function events: deletions, truncating variants, copy-number loss, and structural events. - Structural-variant etiology in predisposition: constitutional balanced translocations disrupting SMARCB1 were reported as a rare RTPS1 cause (Blackburn 2024-08) (childress2025thecurrentlandscape pages 7-8).
A widely accepted methylation/transcriptomic stratification includes: - ATRT-TYR, ATRT-SHH, ATRT-MYC (SMARCB1-mutant majority) (tran2023currentadvancesin pages 1-2, holdhof2021atypicalteratoidrhabdoidtumors pages 1-2) - ATRT-SMARCA4 as a distinct methylation-defined group (holdhof2021atypicalteratoidrhabdoidtumors pages 1-2, johann2023recurrentatypicalteratoidrhabdoid pages 1-2)
Clinical correlates include distinct age and anatomic predilections (Tran 2023-01; Holdhof 2021-12) (tran2023currentadvancesin pages 1-2, holdhof2021atypicalteratoidrhabdoidtumors pages 1-2).
Based on SWI/SNF and epigenetic-differentiation blockade (conceptual mapping; validate in GO): - GO:0016585 chromatin remodeling - GO:0006355 regulation of transcription, DNA-templated - GO:0045893 positive regulation of transcription, DNA-templated (developmental programs suppressed) - GO:0045165 cell fate commitment / differentiation processes (blocked) (huhtala2024developmentandepigenetic pages 1-2)
No environmental, lifestyle, or infectious causal factors were identified in the retrieved evidence set; ATRT is primarily a genetically and epigenetically driven pediatric cancer (huhtala2024developmentandepigenetic pages 1-2, holdhof2021atypicalteratoidrhabdoidtumors pages 1-2).
A matched primary–recurrence cohort found progression-associated but relatively subtle molecular changes. Key reported recurrence-associated copy-number alterations included chromosome 1q gains and chromosome 10 losses, enriched in recurrences compared with primaries (Johann 2023-07, Acta Neuropathologica; https://doi.org/10.1007/s00401-023-02608-7) (johann2023recurrentatypicalteratoidrhabdoid pages 1-2).
A 2023 organoid/tumoroid model paper reported subgroup-specific vulnerabilities: “High throughput drug screens…revealed distinct drug sensitivities… Whereas ATRT-MYC universally displayed high sensitivity to multi-targeted tyrosine kinase inhibitors, ATRT-SHH showed a more heterogeneous response with a subset showing high sensitivity to NOTCH inhibitors…” (Paassen 2023-04) (reddy2020efficacyofhighdose pages 1-2). This supports subgroup-aware treatment development.
ATRT immune profiles differ by subgroup; ATRT-MYC is described as having higher CD8+ tumor-infiltrating lymphocytes and possible immunogenic potential (Tran 2023-01) (tran2023currentadvancesin pages 1-2).
No single-cell dataset was retrieved in this run; however, based on immune infiltration discussions: - CL:0000623 CD8-positive, alpha-beta T cell (ATRT-MYC enriched) (tran2023currentadvancesin pages 1-2) - CL:0000540 neuron / CL:0000127 astrocyte lineage cells (developmental programs implicated) (huhtala2024developmentandepigenetic pages 1-2)
ATRT arises throughout the neuraxis, including supratentorial, infratentorial, pineal, and spinal compartments. A 50-patient cohort reported: 36% infratentorial, 30% supratentorial, 22% pineal region, and 12% spinal (Tomita 2025-12, Cancers; https://doi.org/10.3390/cancers18010008) (tomita2025histogenesisofatypical pages 1-2).
(UBERON IDs are suggested for structuring; the retrieved evidence supports the anatomic compartments but does not provide ontology IDs.)
Typical onset is pediatric, commonly <3 years; ATRT is described as most common malignant brain tumor manifesting in infancy (Johann 2023-07) (johann2023recurrentatypicalteratoidrhabdoid pages 1-2) and “typically affect[s] children younger than 3 years of age” (Tran 2023-01) (tran2023currentadvancesin pages 1-2).
ATRT is characterized by rapid progression and high recurrence risk. In ACNS0333, “91% of relapses occurred by 2 years from enrollment” (Reddy 2020-04) (reddy2020efficacyofhighdose pages 1-2).
RTPS is inherited via germline pathogenic variants in SMARCB1 (RTPS1) or SMARCA4 (RTPS2) and confers risk for multiple rhabdoid tumors (Blackburn 2024-08; Geethadevi 2024-09) (childress2025thecurrentlandscape pages 7-8, reddy2020efficacyofhighdose media 822317c7). Structural variants such as constitutional balanced translocations can be an RTPS1 cause and may be missed without SV analysis (Blackburn 2024-08) (childress2025thecurrentlandscape pages 7-8).
A key routine diagnostic principle is nuclear loss of INI1 and/or BRG1: - “INI-1 (SMARCB1) and BRG-1 (SMARCA4) are routine surrogates — ‘As all nucleated cells should express INI-1 and BRG-1,’ and loss of nuclear expression of either should prompt AT/RT diagnosis.” (Smith 2025-11, Cancers; https://doi.org/10.3390/cancers17233768) (smith2025atypicalteratoidrhabdoid pages 4-7).
MRI features include restricted diffusion, cystic/necrotic change, and hemorrhage; CT lesions can be hyperdense with calcifications (Smith 2025-11) (smith2025atypicalteratoidrhabdoid pages 2-4).
Not fully extracted in this run; however, diagnostic challenge is recognized and motivates multimodal diagnostic integration (smith2025atypicalteratoidrhabdoid pages 4-7).
Children’s Oncology Group ACNS0333 (prospective cooperative-group trial): - “Four-year EFS and overall survival for the entire cohort were 37%… and 43%…” (Reddy 2020-04) (reddy2020efficacyofhighdose pages 1-2). - Regimen significantly reduced EFS events in patients <36 months vs historical cohort (hazard rate 0.43; P<.0005) (Reddy 2020-04) (reddy2020efficacyofhighdose pages 1-2).
Clinical prognostic factors (from reviews): metastatic disease at diagnosis is common (~20–40%) and often adverse; extent of resection and radiotherapy are variably associated with better outcomes (Childress 2025-06) (childress2025thecurrentlandscape pages 7-8).
ATRT is treated with intensive multimodal therapy including maximal safe surgical resection, multiagent chemotherapy, radiotherapy (often focal; CSI for select metastatic cases/age contexts), and high-dose chemotherapy with autologous stem cell rescue in many protocols.
ACNS0333 protocol (widely used backbone): - Induction chemotherapy, consolidation with high-dose chemotherapy and PBSC rescue, plus involved-field radiation; reported 4-year OS 43% (Reddy 2020-04) (reddy2020efficacyofhighdose pages 1-2). - Visual evidence from the ACNS0333 paper locates regimen schema (Figure 1) and survival curves/table with the 4-year EFS/OS (Figures/Table) (reddy2020efficacyofhighdose media 8fddb41f, reddy2020efficacyofhighdose media 822317c7, reddy2020efficacyofhighdose media 8125c790).
Suggested MAXO terms (examples; validate): - Surgical tumor resection (MAXO: surgical excision) - Antineoplastic chemotherapy (multiagent chemotherapy; high-dose chemotherapy) - Radiotherapy (involved-field radiotherapy; craniospinal irradiation) - Autologous hematopoietic stem cell transplantation / stem cell rescue
Immunotherapy landscape: A 2023 review highlights immunotherapy as a response to poor outcomes and toxicity: “there is an urgent need for more novel approaches to treat ATRT, one such approach being immunotherapy.” (Tran 2023-01) (tran2023currentadvancesin pages 1-2).
EZH2 inhibition (tazemetostat) and combinations: - NCT02601937 (Phase 1; COMPLETED; results first posted 2024-10-03): pediatric tazemetostat in relapsed/refractory INI1-negative tumors including ATRT; ATRT expansion cohort regimen reported as 1200 mg/m^2 BID continuous 28-day cycles (ClinicalTrials.gov; https://clinicaltrials.gov/study/NCT02601937) (NCT02601937 chunk 1, NCT02601937 chunk 2). - NCT05407441 (Phase I/II; ACTIVE_NOT_RECRUITING; start 2023-08-10): tazemetostat + nivolumab + ipilimumab for INI1-negative/SMARCA4-deficient tumors including ATRT (ClinicalTrials.gov; https://clinicaltrials.gov/study/NCT05407441) (NCT05407441 chunk 1). - NCT03838042 (Phase I/II; RECRUITING): nivolumab + entinostat in biomarker-defined cohorts including ATRT-MYC (ClinicalTrials.gov; https://clinicaltrials.gov/study/NCT03838042) (NCT03838042 chunk 1).
HDAC inhibition (panobinostat): - NCT04897880 (Phase 2; TERMINATED due to drug supply): panobinostat in pediatric solid tumors including MRT/ATRT (ClinicalTrials.gov; https://clinicaltrials.gov/study/NCT04897880) (NCT04897880 chunk 1).
No established primary prevention is known for sporadic ATRT, given its early-life onset and tumor-suppressor loss mechanism.
RTPS is a key context where prevention-oriented strategies are discussed. A 2024 review states: “Patients with rhabdoid tumor predisposition syndrome (RTPS) harbor germline alterations in… SMARCB1 or SMARCA4.” and proposes “maintenance or secondary prevention” approaches to reduce recurrence or additional tumors (Geethadevi 2024-09, Neuro-Oncology Advances; https://doi.org/10.1093/noajnl/vdae158) (reddy2020efficacyofhighdose media 822317c7).
No naturally occurring ATRT analogs in non-human species were identified in the retrieved evidence set.
A 2023 study established ATRT “tumoroid models” from ATRT-MYC and ATRT-SHH that retained subgroup epigenetic/transcriptomic profiles and enabled high-throughput drug screening, revealing subgroup-specific sensitivities (Paassen 2023-04) (reddy2020efficacyofhighdose pages 1-2). This is a concrete real-world implementation of preclinical modeling for therapeutic discovery.
The following table consolidates core definitions, subgroups, diagnostics, treatments, outcomes, and 2023–2024 developments:
| Topic | Key details | Evidence / source |
|---|---|---|
| Definition / classification | Atypical teratoid/rhabdoid tumor (ATRT; also AT/RT) is a rare, highly aggressive embryonal CNS tumor, predominantly of infancy/early childhood; WHO-classified as an embryonal CNS neoplasm. It accounts for ~1–2% of pediatric CNS tumors overall, but ~20% of CNS tumors in children <3 years; median age at diagnosis ~16–30 months. ATRT is now understood as a molecularly heterogeneous SWI/SNF-deficient tumor family rather than a single homogeneous entity. | Tran 2023, Neuro-Oncology Practice, Jan 2023, https://doi.org/10.1093/nop/npad005; Tomita 2025, Cancers, Dec 2025, https://doi.org/10.3390/cancers18010008 (tran2023currentadvancesin pages 1-2, tomita2025histogenesisofatypical pages 2-4) |
| Hallmark genes / protein surrogates | Defining event: biallelic loss/inactivation of SMARCB1 in ~95% of cases; rare SMARCA4-mutant cases (~0.5–2%, some series up to ~4%). Routine diagnostic protein surrogates are loss of nuclear INI1/BAF47 for SMARCB1-deficient tumors and loss of BRG1 for SMARCA4-deficient tumors; all nucleated cells should normally express both. Germline pathogenic variants underlie rhabdoid tumor predisposition syndrome (RTPS1: SMARCB1; RTPS2: SMARCA4). | Holdhof 2021, Acta Neuropathologica, Dec 2021, https://doi.org/10.1007/s00401-020-02250-7; Smith 2025, Cancers, Nov 2025, https://doi.org/10.3390/cancers17233768; Blackburn 2024, Genes Chromosomes Cancer, Aug 2024, https://doi.org/10.1002/gcc.23195 (holdhof2021atypicalteratoidrhabdoidtumors pages 1-2, smith2025atypicalteratoidrhabdoid pages 4-7, childress2025thecurrentlandscape pages 7-8) |
| Molecular subgroup: ATRT-TYR | TYR subgroup: tends to occur in the youngest patients (often 0–1 year), commonly infratentorial, with overexpression of melanocytic / melanosomal genes (TYR, TYRP1, MITF, OTX2). Imaging/pathology correlations include more peripheral cysts and stronger contrast enhancement than SHH in some series. | Tran 2023, https://doi.org/10.1093/nop/npad005; Smith 2025, https://doi.org/10.3390/cancers17233768 (tran2023currentadvancesin pages 1-2, smith2025atypicalteratoidrhabdoid pages 2-4) |
| Molecular subgroup: ATRT-SHH | SHH subgroup: mixed supra- and infratentorial distribution overall; enriched for SHH/NOTCH-related programs and genes such as GLI2, BOC, PTCHD2, MYCN. Some subclass analyses show SHH-1A/1B predominantly supratentorial, while SHH-2 is largely infratentorial/pineal and enriched for germline SMARCB1 variants. Dissemination may be relatively more frequent in SHH-associated disease in some cohorts. | Tran 2023, https://doi.org/10.1093/nop/npad005; Tomita 2025, https://doi.org/10.3390/cancers18010008; Smith 2025, https://doi.org/10.3390/cancers17233768 (tran2023currentadvancesin pages 1-2, tomita2025histogenesisofatypical pages 14-15, smith2025atypicalteratoidrhabdoid pages 2-4) |
| Molecular subgroup: ATRT-MYC | MYC subgroup: often supratentorial; overexpresses MYC and HOX-related programs; a subset arises extra-axially, including along cranial nerves. Compared with other subgroups, ATRT-MYC has been reported to show higher CD8+ tumor-infiltrating lymphocytes, supporting relative immunogenicity. | Tran 2023, https://doi.org/10.1093/nop/npad005; Smith 2025, https://doi.org/10.3390/cancers17233768 (tran2023currentadvancesin pages 1-2, smith2025atypicalteratoidrhabdoid pages 2-4) |
| Molecular subgroup: ATRT-SMARCA4 | Rare, molecularly distinct subgroup defined by SMARCA4 loss rather than SMARCB1 loss; retains INI1 expression but loses BRG1. Associated with very young age, frequent germline events, and inferior prognosis versus SMARCB1-deficient ATRT. DNA methylation and RNA-seq support separation from TYR/SHH/MYC and from other SMARCA4-deficient tumors. | Holdhof 2021, https://doi.org/10.1007/s00401-020-02250-7; Tomita 2025, https://doi.org/10.3390/cancers18010008 (holdhof2021atypicalteratoidrhabdoidtumors pages 1-2, tomita2025histogenesisofatypical pages 14-15) |
| Typical anatomy / presentation | ATRT can arise anywhere along the neuraxis. In one 50-patient pediatric cohort: 36% infratentorial, 30% supratentorial, 22% pineal region, 12% spinal. Posterior fossa is common, often off-midline. Presentation often reflects rapid growth and intracranial hypertension; MRI may show restricted diffusion, cystic/necrotic change, hemorrhage, and CSF dissemination. Metastatic disease is present in ~20–40% at diagnosis; one review cited M1 CSF positivity around 38%. | Tomita 2025, https://doi.org/10.3390/cancers18010008; Childress 2025, https://doi.org/10.3390/jmp6020013; Smith 2025, https://doi.org/10.3390/cancers17233768; Hoffman 2020, https://doi.org/10.1093/neuonc/noaa046 (tomita2025histogenesisofatypical pages 1-2, childress2025thecurrentlandscape pages 7-8, smith2025atypicalteratoidrhabdoid pages 2-4, hoffman2020advancingbiologybased pages 4-5) |
| Diagnostic modalities | Modern diagnosis integrates histology + IHC + molecular testing. Core methods: (1) histopathology showing rhabdoid morphology with variable epithelial/mesenchymal/neuroectodermal elements; (2) IHC for INI1/SMARCB1 and BRG1/SMARCA4 loss; (3) genome-wide DNA methylation profiling, now considered highly informative / WHO-essential in difficult cases for subgroup assignment; (4) sequencing / CNV analysis for SMARCB1 or SMARCA4 alterations; (5) FISH / copy-number methods for 22q11.2 SMARCB1 loss when needed. | Smith 2025, https://doi.org/10.3390/cancers17233768; Holdhof 2021, https://doi.org/10.1007/s00401-020-02250-7; Childress 2025, https://doi.org/10.3390/jmp6020013 (smith2025atypicalteratoidrhabdoid pages 4-7, holdhof2021atypicalteratoidrhabdoidtumors pages 1-2, childress2025thecurrentlandscape pages 10-12) |
| Standard therapy backbone (ACNS0333) | Contemporary backbone is aggressive multimodal therapy: maximal safe resection, intensive induction chemotherapy, focal/involved-field radiotherapy, then high-dose chemotherapy with autologous stem-cell rescue. ACNS0333 schema: 2 induction cycles including vincristine, methotrexate, etoposide, cyclophosphamide, cisplatin; then 3 consolidation cycles with thiotepa + carboplatin and PBSC rescue; focal RT timing adapted by age/disease status. Gross total resection is achieved in ~30–68% across series. | Reddy 2020, JCO, Apr 2020, https://doi.org/10.1200/JCO.19.01776; figure/table locations summarized from ACNS0333 visual review (reddy2020efficacyofhighdose pages 1-2, reddy2020efficacyofhighdose media 8fddb41f, childress2025thecurrentlandscape pages 7-8) |
| Key outcome statistics | ACNS0333 (65 evaluable patients): 4-year EFS 37% (95% CI 25–49) and 4-year OS 43% (95% CI 31–55); for patients <36 months, EFS hazard ratio vs historical cohort 0.43 (P<.0005). 91% of relapses occurred within 2 years; treatment-related deaths: 4. Other cited multimodal results: Dana-Farber regimen 2-year EFS/OS 53%/70%; Head Start HDCT/ASCR 3-year EFS/OS 21%/26%. | Reddy 2020, https://doi.org/10.1200/JCO.19.01776; Childress 2025, https://doi.org/10.3390/jmp6020013 (reddy2020efficacyofhighdose pages 1-2, childress2025thecurrentlandscape pages 7-8) |
| Representative mechanistic findings (2023–2024) | Recurrence biology: recurrent ATRTs show increased mitotic activity, occasional subgroup switching, and enrichment of chromosome 1q gain and chromosome 10 loss; primary and relapse usually remain close by methylation/transcriptome, implying relative epigenetic stability with selected progression-associated changes. Epigenetic differentiation blockade: AT/RT-specific DNA hypermethylation is linked to PRC2, suppression of neural differentiation genes, impaired NEUROG/NEUROD pioneer-factor activity, and maintenance of a low-differentiation malignant state. Model systems / vulnerabilities: 2023 tumoroid models retained subgroup-specific epigenetic states; ATRT-MYC showed broad sensitivity to multi-targeted tyrosine kinase inhibitors, while a subset of ATRT-SHH was sensitive to NOTCH inhibitors. | Johann 2023, Acta Neuropathologica, Jul 2023, https://doi.org/10.1007/s00401-023-02608-7; Pekkarinen 2024, Life Science Alliance, Mar 2024, https://doi.org/10.26508/lsa.202302088; Paassen 2023, Oncogene, Apr 2023, https://doi.org/10.1038/s41388-023-02681-y; Huhtala 2024, Neuro-Oncology Advances, Sep 2024, https://doi.org/10.1093/noajnl/vdae162 (johann2023recurrentatypicalteratoidrhabdoid pages 1-2, huhtala2024developmentandepigenetic pages 1-2, reddy2020efficacyofhighdose pages 1-2) |
| Immune microenvironment / translational rationale | ATRT is epigenetically driven but immunologically nonuniform across subgroups; ATRT-MYC has relatively higher CD8+ infiltration, motivating immune-based strategies. Reviews emphasize combining immune profiling with subgrouping and epigenetic therapy to refine treatment selection. | Tran 2023, https://doi.org/10.1093/nop/npad005; Childress 2025, https://doi.org/10.3390/jmp6020013 (tran2023currentadvancesin pages 1-2, childress2025thecurrentlandscape pages 10-12) |
| Representative clinical trials | NCT02601937 — tazemetostat (EZH2 inhibitor), Phase 1, completed, pediatric relapsed/refractory INI1-negative tumors including ATRT; results posted 2024-10-03; ATRT cohort used 1200 mg/m² BID continuous 28-day cycles. NCT05407441 — tazemetostat + nivolumab + ipilimumab, Phase I/II, Active not recruiting, ATRT / INI1-negative / SMARCA4-deficient tumors. NCT04416568 — nivolumab + ipilimumab in INI1-negative cancers, Phase 2, Active not recruiting. NCT04897880 — panobinostat in pediatric solid tumors including MRT/ATRT, Phase 2, Terminated (drug supply). NCT03838042 — INFORM2 Nivolumab + entinostat, Phase I/II, Recruiting; includes biomarker-defined cohorts including ATRT-MYC. | ClinicalTrials.gov records summarized from extracted trial evidence (NCT02601937, NCT05407441, NCT04416568, NCT04897880, NCT03838042) (NCT04897880 chunk 1, NCT02601937 chunk 2, NCT05407441 chunk 1, NCT02601937 chunk 1, NCT03838042 chunk 1) |
Table: This table condenses the most clinically and biologically relevant facts about ATRT, including defining molecular features, subgroup correlates, diagnostics, standard therapy, outcomes, and representative recent research and trials. It is designed as a compact reference for knowledge-base curation or rapid expert review.
References
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(reddy2020efficacyofhighdose pages 1-2): Alyssa T. Reddy, Douglas R. Strother, Alexander R. Judkins, Peter C. Burger, Ian F. Pollack, Mark D. Krailo, Allen B. Buxton, Chris Williams-Hughes, Maryam Fouladi, Anita Mahajan, Thomas E. Merchant, Ben Ho, Claire M. Mazewski, Victor A. Lewis, Amar Gajjar, Louis-Gilbert Vezina, Timothy N. Booth, Kerry W. Parsons, Vicky L. Poss, Tianni Zhou, Jaclyn A. Biegel, and Annie Huang. Efficacy of high-dose chemotherapy and three-dimensional conformal radiation for atypical teratoid/rhabdoid tumor: a report from the children’s oncology group trial acns0333. Journal of Clinical Oncology, 38:1175-1185, Apr 2020. URL: https://doi.org/10.1200/jco.19.01776, doi:10.1200/jco.19.01776. This article has 238 citations and is from a highest quality peer-reviewed journal.
(holdhof2021atypicalteratoidrhabdoidtumors pages 1-2): Dörthe Holdhof, Pascal D. Johann, Michael Spohn, Michael Bockmayr, Sepehr Safaei, Piyush Joshi, Julien Masliah-Planchon, Ben Ho, Mamy Andrianteranagna, Franck Bourdeaut, Annie Huang, Marcel Kool, Santhosh A. Upadhyaya, Anne E. Bendel, Daniela Indenbirken, William D. Foulkes, Jonathan W. Bush, David Creytens, Uwe Kordes, Michael C. Frühwald, Martin Hasselblatt, and Ulrich Schüller. Atypical teratoid/rhabdoid tumors (atrts) with smarca4 mutation are molecularly distinct from smarcb1-deficient cases. Acta Neuropathologica, 141:291-301, Dec 2021. URL: https://doi.org/10.1007/s00401-020-02250-7, doi:10.1007/s00401-020-02250-7. This article has 110 citations and is from a highest quality peer-reviewed journal.
(smith2025atypicalteratoidrhabdoid pages 4-7): Heather L. Smith, Pascale Aouad, and Nitin R. Wadhwani. Atypical teratoid rhabdoid tumor: how tumor diagnostic methods in the laboratory have evolved over the past 40 years. Cancers, 17:3768, Nov 2025. URL: https://doi.org/10.3390/cancers17233768, doi:10.3390/cancers17233768. This article has 1 citations.
(childress2025thecurrentlandscape pages 7-8): Ashley Childress, Alayna Koch, Emma Vallee, Alyssa Steller, and Scott Raskin. The current landscape of molecular pathology for the diagnosis and treatment of atypical teratoid rhabdoid tumor. Journal of Molecular Pathology, 6:13, Jun 2025. URL: https://doi.org/10.3390/jmp6020013, doi:10.3390/jmp6020013. This article has 0 citations.
(tomita2025histogenesisofatypical pages 14-15): Tadanori Tomita. Histogenesis of atypical teratoid rhabdoid tumors: anatomical and embryological perspectives. Cancers, 18:8, Dec 2025. URL: https://doi.org/10.3390/cancers18010008, doi:10.3390/cancers18010008. This article has 0 citations.
(huhtala2024developmentandepigenetic pages 1-2): Laura Huhtala, Goktug Karabiyik, and Kirsi J Rautajoki. Development and epigenetic regulation of atypical teratoid/rhabdoid tumors in the context of cell-of-origin and halted cell differentiation. Neuro-Oncology Advances, Sep 2024. URL: https://doi.org/10.1093/noajnl/vdae162, doi:10.1093/noajnl/vdae162. This article has 9 citations and is from a peer-reviewed journal.
(smith2025atypicalteratoidrhabdoid pages 2-4): Heather L. Smith, Pascale Aouad, and Nitin R. Wadhwani. Atypical teratoid rhabdoid tumor: how tumor diagnostic methods in the laboratory have evolved over the past 40 years. Cancers, 17:3768, Nov 2025. URL: https://doi.org/10.3390/cancers17233768, doi:10.3390/cancers17233768. This article has 1 citations.
(johann2023recurrentatypicalteratoidrhabdoid pages 1-2): Pascal D. Johann, Lea Altendorf, Emma-Maria Efremova, Till Holsten, Mona Steinbügl, Karolina Nemes, Alicia Eckhardt, Catena Kresbach, Michael Bockmayr, Arend Koch, Christine Haberler, Manila Antonelli, John DeSisto, Martin U. Schuhmann, Peter Hauser, Reiner Siebert, Susanne Bens, Marcel Kool, Adam L. Green, Martin Hasselblatt, Michael C. Frühwald, and Ulrich Schüller. Recurrent atypical teratoid/rhabdoid tumors (at/rt) reveal discrete features of progression on histology, epigenetics, copy number profiling, and transcriptomics. Acta Neuropathologica, 146:527-541, Jul 2023. URL: https://doi.org/10.1007/s00401-023-02608-7, doi:10.1007/s00401-023-02608-7. This article has 20 citations and is from a highest quality peer-reviewed journal.
(tomita2025histogenesisofatypical pages 1-2): Tadanori Tomita. Histogenesis of atypical teratoid rhabdoid tumors: anatomical and embryological perspectives. Cancers, 18:8, Dec 2025. URL: https://doi.org/10.3390/cancers18010008, doi:10.3390/cancers18010008. This article has 0 citations.
(reddy2020efficacyofhighdose media 822317c7): Alyssa T. Reddy, Douglas R. Strother, Alexander R. Judkins, Peter C. Burger, Ian F. Pollack, Mark D. Krailo, Allen B. Buxton, Chris Williams-Hughes, Maryam Fouladi, Anita Mahajan, Thomas E. Merchant, Ben Ho, Claire M. Mazewski, Victor A. Lewis, Amar Gajjar, Louis-Gilbert Vezina, Timothy N. Booth, Kerry W. Parsons, Vicky L. Poss, Tianni Zhou, Jaclyn A. Biegel, and Annie Huang. Efficacy of high-dose chemotherapy and three-dimensional conformal radiation for atypical teratoid/rhabdoid tumor: a report from the children’s oncology group trial acns0333. Journal of Clinical Oncology, 38:1175-1185, Apr 2020. URL: https://doi.org/10.1200/jco.19.01776, doi:10.1200/jco.19.01776. This article has 238 citations and is from a highest quality peer-reviewed journal.
(reddy2020efficacyofhighdose media 8fddb41f): Alyssa T. Reddy, Douglas R. Strother, Alexander R. Judkins, Peter C. Burger, Ian F. Pollack, Mark D. Krailo, Allen B. Buxton, Chris Williams-Hughes, Maryam Fouladi, Anita Mahajan, Thomas E. Merchant, Ben Ho, Claire M. Mazewski, Victor A. Lewis, Amar Gajjar, Louis-Gilbert Vezina, Timothy N. Booth, Kerry W. Parsons, Vicky L. Poss, Tianni Zhou, Jaclyn A. Biegel, and Annie Huang. Efficacy of high-dose chemotherapy and three-dimensional conformal radiation for atypical teratoid/rhabdoid tumor: a report from the children’s oncology group trial acns0333. Journal of Clinical Oncology, 38:1175-1185, Apr 2020. URL: https://doi.org/10.1200/jco.19.01776, doi:10.1200/jco.19.01776. This article has 238 citations and is from a highest quality peer-reviewed journal.
(reddy2020efficacyofhighdose media 8125c790): Alyssa T. Reddy, Douglas R. Strother, Alexander R. Judkins, Peter C. Burger, Ian F. Pollack, Mark D. Krailo, Allen B. Buxton, Chris Williams-Hughes, Maryam Fouladi, Anita Mahajan, Thomas E. Merchant, Ben Ho, Claire M. Mazewski, Victor A. Lewis, Amar Gajjar, Louis-Gilbert Vezina, Timothy N. Booth, Kerry W. Parsons, Vicky L. Poss, Tianni Zhou, Jaclyn A. Biegel, and Annie Huang. Efficacy of high-dose chemotherapy and three-dimensional conformal radiation for atypical teratoid/rhabdoid tumor: a report from the children’s oncology group trial acns0333. Journal of Clinical Oncology, 38:1175-1185, Apr 2020. URL: https://doi.org/10.1200/jco.19.01776, doi:10.1200/jco.19.01776. This article has 238 citations and is from a highest quality peer-reviewed journal.
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(NCT02601937 chunk 2): EZH2 Inhibitor Tazemetostat in Pediatric Subjects With Relapsed or Refractory INI1-Negative Tumors or Synovial Sarcoma. Epizyme, Inc.. 2016. ClinicalTrials.gov Identifier: NCT02601937
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(tomita2025histogenesisofatypical pages 2-4): Tadanori Tomita. Histogenesis of atypical teratoid rhabdoid tumors: anatomical and embryological perspectives. Cancers, 18:8, Dec 2025. URL: https://doi.org/10.3390/cancers18010008, doi:10.3390/cancers18010008. This article has 0 citations.
(hoffman2020advancingbiologybased pages 4-5): Lindsey M Hoffman, Elizabeth Anne Richardson, Ben Ho, Ashley Margol, Alyssa Reddy, Lucie Lafay-Cousin, Susan Chi, Irene Slavc, Alexander Judkins, Martin Hasselblatt, Franck Bourdeaut, Michael C Frühwald, Rajeev Vibhakar, Eric Bouffet, and Annie Huang. Advancing biology based therapeutic approaches for atypical teratoid rhabdoid tumors. Neuro-oncology, 22:944-954, Mar 2020. URL: https://doi.org/10.1093/neuonc/noaa046, doi:10.1093/neuonc/noaa046. This article has 39 citations and is from a domain leading peer-reviewed journal.
(childress2025thecurrentlandscape pages 10-12): Ashley Childress, Alayna Koch, Emma Vallee, Alyssa Steller, and Scott Raskin. The current landscape of molecular pathology for the diagnosis and treatment of atypical teratoid rhabdoid tumor. Journal of Molecular Pathology, 6:13, Jun 2025. URL: https://doi.org/10.3390/jmp6020013, doi:10.3390/jmp6020013. This article has 0 citations.