DNA methylation data from 153 ATRT tumor samples
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PROVIDER: PRJNA591854 | ENA |
REPOSITORIES: ENA
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Project description:Clinical and molecular risk factors were analyzed in a large cohort of patients with Atypical Teratoid Rhabdoid Tumors (ATRT) recruited to the European Rhabdoid Regsitry (EU-RHAB) and data were validated in a second independent cohort of ATRT patients.
2020-01-31 | GSE141039 | GEO
Project description:DNA methylation data from 13 ATRT tumor samples
| PRJNA594629 | ENA
Project description:Atypical teratoid/rhabdoid tumor (ATRT) is one of the most common brain tumors in infants. Although the prognosis of ATRT patients is poor, some patients respond favorably to current treatments, suggesting molecular inter-tumor heterogeneity. To investigate this further, we genetically and epigenetically analyzed a large series of human ATRTs. Three distinct molecular subgroups of ATRTs, associated with differences in demographics, tumor location, and type of SMARCB1 alterations, were identified. Whole-genome DNA and RNA sequencing found no recurrent mutations in addition to SMARCB1 that would explain the differences between subgroups. 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. 49 ATRT samples were selected for RNA extraction and hybridization on Affymetrix Affymetrix Human Genome U133 Plus 2.0 Arrays. ---------------------------------------- This submission consists of the expression data for 49 of 170 samples only
2016-03-02 | E-GEOD-70678 | biostudies-arrayexpress
Project description:The samples deposited here are part of the ATRT consensus cohort as published in Ho et al. ("Molecular subgrouping of Atypical Teratoid/Rhabdoid Tumors (ATRT) - a reinvestigation and current consensus") and have so far not been included in any publication.
2020-01-31 | GSE141363 | GEO
Project description:Atypical teratoid/rhabdoid tumor (ATRT) is one of the most common brain tumors in infants. Although the prognosis of ATRT patients is poor, some patients respond favorably to current treatments, suggesting molecular inter-tumor heterogeneity. To investigate this further, we genetically and epigenetically analyzed a large series of human ATRTs. Three distinct molecular subgroups of ATRTs, associated with differences in demographics, tumor location, and type of SMARCB1 alterations, were identified. Whole-genome DNA and RNA sequencing found no recurrent mutations in addition to SMARCB1 that would explain the differences between subgroups. 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.
2016-03-02 | GSE70678 | GEO
Project description:Atypical teratoid rhabdoid tumor (ATRT) is a highly aggressive but genetically simple pediatric central nervous system tumor, defined by biallelic inactivation of the chromatin regulator SMARCB1 with remarkably few other cooperating mutations. Despite its genetic homogeneity, ATRT exhibits profound clinical and epigenetic heterogeneity, with three major subgroups (ATRT-TYR, ATRT-MYC, and ATRT-SHH) defined by DNA methylation and transcriptional signatures. Beyond these subgroup-defining features, we aimed to investigate epigenetic variability within tumors by applying whole-genome bisulfite sequencing and probabilistic modeling to quantify stochastic DNA methylation in primary ATRT samples encompassing all three subgroups. We show that ATRT exhibits a destabilized and increasingly stochastic methylome. While ATRT global methylation patterns diverge according to subgroup, some methylation perturbations, such as hypermethylation and increased methylation entropy over bivalent promoters, are consistent across subgroups. We find that methylation stochasticity alterations map onto potential drivers of ATRT, such as LIN28a, the HOXD cluster for ATRT-MYC, and OTX2 for ATRT-TYR, and identify actionable targets, such as hypermethylation of the tumor suppressor CDKN2a across all subgroups. We investigate the sensitivity of the aberrant DNA methylation landscape of ATRT to pharmacologic DNA methyltransferase inhibition and histone deacetylase inhibition (HDACi). We show that decitabine leads to profound demethylation of patient-derived ATRT cell lines, including reversal of hypermethylation at bivalent promoters and the CDKN2a locus. The addition of HDACi leads to dramatic gene expression changes, including upregulation of innate immune signaling pathways, such as STING/interferon signaling, genes under the regulation of bivalent promoters, and reactivation of the tumor suppressor CDKN2A. The combination of DNMTi and HDACi synergistically reduces cell viability. Taken together, we show that ATRT has a highly stochastic methylome sensitive to epigenetic manipulation.
2025-11-14 | GSE301412 | GEO
Project description:Atypical teratoid rhabdoid tumor (ATRT) is a highly aggressive but genetically simple pediatric central nervous system tumor, defined by biallelic inactivation of the chromatin regulator SMARCB1 with remarkably few other cooperating mutations. Despite its genetic homogeneity, ATRT exhibits profound clinical and epigenetic heterogeneity, with three major subgroups (ATRT-TYR, ATRT-MYC, and ATRT-SHH) defined by DNA methylation and transcriptional signatures. Beyond these subgroup-defining features, we aimed to investigate epigenetic variability within tumors by applying whole-genome bisulfite sequencing and probabilistic modeling to quantify stochastic DNA methylation in primary ATRT samples encompassing all three subgroups. We show that ATRT exhibits a destabilized and increasingly stochastic methylome. While ATRT global methylation patterns diverge according to subgroup, some methylation perturbations, such as hypermethylation and increased methylation entropy over bivalent promoters, are consistent across subgroups. We find that methylation stochasticity alterations map onto potential drivers of ATRT, such as LIN28a, the HOXD cluster for ATRT-MYC, and OTX2 for ATRT-TYR, and identify actionable targets, such as hypermethylation of the tumor suppressor CDKN2a across all subgroups. We investigate the sensitivity of the aberrant DNA methylation landscape of ATRT to pharmacologic DNA methyltransferase inhibition and histone deacetylase inhibition (HDACi). We show that decitabine leads to profound demethylation of patient-derived ATRT cell lines, including reversal of hypermethylation at bivalent promoters and the CDKN2a locus. The addition of HDACi leads to dramatic gene expression changes, including upregulation of innate immune signaling pathways, such as STING/interferon signaling, genes under the regulation of bivalent promoters, and reactivation of the tumor suppressor CDKN2A. The combination of DNMTi and HDACi synergistically reduces cell viability. Taken together, we show that ATRT has a highly stochastic methylome sensitive to epigenetic manipulation.
2025-11-14 | GSE301405 | GEO
Project description:Atypical teratoid rhabdoid tumor (ATRT) is a highly aggressive but genetically simple pediatric central nervous system tumor, defined by biallelic inactivation of the chromatin regulator SMARCB1 with remarkably few other cooperating mutations. Despite its genetic homogeneity, ATRT exhibits profound clinical and epigenetic heterogeneity, with three major subgroups (ATRT-TYR, ATRT-MYC, and ATRT-SHH) defined by DNA methylation and transcriptional signatures. Beyond these subgroup-defining features, we aimed to investigate epigenetic variability within tumors by applying whole-genome bisulfite sequencing and probabilistic modeling to quantify stochastic DNA methylation in primary ATRT samples encompassing all three subgroups. We show that ATRT exhibits a destabilized and increasingly stochastic methylome. While ATRT global methylation patterns diverge according to subgroup, some methylation perturbations, such as hypermethylation and increased methylation entropy over bivalent promoters, are consistent across subgroups. We find that methylation stochasticity alterations map onto potential drivers of ATRT, such as LIN28a, the HOXD cluster for ATRT-MYC, and OTX2 for ATRT-TYR, and identify actionable targets, such as hypermethylation of the tumor suppressor CDKN2a across all subgroups. We investigate the sensitivity of the aberrant DNA methylation landscape of ATRT to pharmacologic DNA methyltransferase inhibition and histone deacetylase inhibition (HDACi). We show that decitabine leads to profound demethylation of patient-derived ATRT cell lines, including reversal of hypermethylation at bivalent promoters and the CDKN2a locus. The addition of HDACi leads to dramatic gene expression changes, including upregulation of innate immune signaling pathways, such as STING/interferon signaling, genes under the regulation of bivalent promoters, and reactivation of the tumor suppressor CDKN2A. The combination of DNMTi and HDACi synergistically reduces cell viability. Taken together, we show that ATRT has a highly stochastic methylome sensitive to epigenetic manipulation.
2025-11-14 | GSE301410 | GEO
Project description:Atypical teratoid/rhabdoid tumors (ATRT) are known for their heterogeneity concerning pathophysiology and outcome. However, predictive factors within distinct subgroups still need to be uncovered. Using multiplex immunofluorescent staining and singe-cell RNA sequencing we unraveled distinct compositions of the immunological tumor microenvironment (TME) across ATRT subgroups. CD68+ cells predominantly infiltrate ATRT-SHH and ATRT-MYC and are a negative prognostic factor for patients’ survival. Within the murine ATRT-MYC and ATRT-SHH TME, Cd68+ macrophages are core to intercellular communication with tumor cells. In ATRT-MYC distinct tumor cell phenotypes express macrophage marker genes. These cells are involved in the acquisition of chemotherapy resistance in our relapse xenograft mouse model. In conclusion, the tumor cell-macrophage interaction contributes to ATRT-MYC heterogeneity and tumor recurrence.
2020-05-14 | GSE141533 | GEO
Project description:Atypical teratoid/rhabdoid tumors (ATRT) are known for their heterogeneity concerning pathophysiology and outcome. However, predictive factors within distinct subgroups still need to be uncovered. Using multiplex immunofluorescent staining and singe-cell RNA sequencing we unraveled distinct compositions of the immunological tumor microenvironment (TME) across ATRT subgroups. CD68+ cells predominantly infiltrate ATRT-SHH and ATRT-MYC and are a negative prognostic factor for patients’ survival. Within the murine ATRT-MYC and ATRT-SHH TME, Cd68+ macrophages are core to intercellular communication with tumor cells. In ATRT-MYC distinct tumor cell phenotypes express macrophage marker genes. These cells are involved in the acquisition of chemotherapy resistance in our relapse xenograft mouse model. In conclusion, the tumor cell-macrophage interaction contributes to ATRT-MYC heterogeneity and tumor recurrence.
2020-05-14 | GSE141532 | GEO