DNA methylation profiles of SMARCB1-deficient T cell lymphomas
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ABSTRACT:
PROVIDER: PRJNA1049496 | ENA |
REPOSITORIES: ENA
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Project description:Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is a heterogeneous group of malignancies with poor outcome. Here we have identified a subgroup of SMARCB1 deficient PTCL-NOS, which is characterized by the lack of the SMARCB1 protein and is more common in young patients. Human and murine Smarcb1-negative PTCL-NOS from a corresponding mouse model show similar DNA methylation profiles, with hypermethylation of T-cell-related genes and hypomethylation of genes involved in myeloid development.
2024-07-16 | GSE249566 | GEO
Project description:SMARCB1 (Snf5/Ini1/Baf47) is a potent tumor suppressor, the loss of which serves as the diagnostic feature in Malignant Rhabdoid Tumors (MRT) and Atypical Teratoid/Rhabdoid Tumors (AT/RT), two highly aggressive forms of pediatric neoplasms. Here, we restore Smarcb1 expression in cells derived from Smarcb1-deficient tumors which developed in Smarcb1-heterozygous p53-/- mice. Profiling Smarcb1 dependent gene expression we find genes which are dependent on Smarcb1 expression to be enriched for ECM and cell adhesion functions. We identify Igfbp7, which is related to the insulin-like growth factor binding proteins family, as a downstream target of Smarcb1 transcriptional activity, and show that re-introduction of Igfbp7 alone can hinder tumor development. Two cancer cell lines, 167 and 365, derived from Smarcb1-deficient tumors which developed in Smarcb1-heterozygous p53-/- mice were re-infected with a retro-viral vector for Smarcb1 re-expression or an empty retro-viral vector as control. Total-RNA was collected 3 days post infection so as to enrich for direct targets of Smarcb1 transcriptionaly regulated genes
2013-12-31 | E-GEOD-46017 | biostudies-arrayexpress
Project description:Single-nuclei gene expression profiling of human SMARCB1-deficient peripheral T cell lymphomas
| PRJNA1069666 | ENA
Project description:We have generated DNA methylation profiles for patient-derived malignant rhabdoid tumor organoids and re-expressed SMARCB1 to assess SMARCB1-dependent changes in DNA methylation
2021-01-13 | GSE161814 | GEO
Project description:Rhabdoid Tumors (RT) are highly aggressive tumors that are frequently localized in the central nervous system (CNS) where they are termed atypical teratoid and rhabdoid tumors (ATRT). We generated conditional Smarcb1-deficient mouse model leads to CNS Smarcb1-deficient tumors. We used microarrays to compared gene expression profilings of various human and mouse tumors. Our data demonstrate that the Smarcb1-deficient mouse model recapitulates the diversity of human RT.
2016-01-27 | GSE64019 | GEO
Project description:SMARCB1 (Snf5/Ini1/Baf47) is a potent tumor suppressor, the loss of which serves as the diagnostic feature in Malignant Rhabdoid Tumors (MRT) and Atypical Teratoid/Rhabdoid Tumors (AT/RT), two highly aggressive forms of pediatric neoplasms. Here, we restore Smarcb1 expression in cells derived from Smarcb1-deficient tumors which developed in Smarcb1-heterozygous p53-/- mice. Profiling Smarcb1 dependent gene expression we find genes which are dependent on Smarcb1 expression to be enriched for ECM and cell adhesion functions. We identify Igfbp7, which is related to the insulin-like growth factor binding proteins family, as a downstream target of Smarcb1 transcriptional activity, and show that re-introduction of Igfbp7 alone can hinder tumor development.
2013-12-31 | GSE46017 | GEO
Project description:Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is a heterogeneous group of malignancies with poor outcome. Here we identified a subgroup, PTCL-NOS SMARCB1-, which is characterized by the lack of SMARCB1 protein expression and is more common in young patients under 25 years of age. To investigate the cellular heterogeneity of PTCL-NOS SMARCB1- and the role of its tumor microenvironment, we performed single-nuclei RNA sequencing (snRNA-seq) of five patient samples.
2024-07-22 | GSE254299 | GEO
Project description:Purpose: Rhabdoid tumors (RTs) are highly aggressive pediatric cancers driven by the biallelic inactivation of the SMARCB1 tumor suppressor gene, the sole recurrent genetic alteration. SMARCB1 encodes a core subunit of the SWI/SNF chromatin remodeling complex; its loss disrupts epigenetic gene regulation, supporting the classification of RTs as prototypical epigenetically driven cancers and highlighting the therapeutic potential of targeting epigenetic modifiers. Notably, previous studies have reported the overexpression of DNMT3A and DNMT3B, enzymes responsible for de novo DNA methylation, in RTs. Experimental Design: Using patient samples, cell lines, and an ex vivo brain organoid system, combined with immunohistochemistry and bioinformatics, we investigated the role of DNMT3 enzymes in RT progression. Results: In a composite tumor case, SMARCB1-deficient and -proficient regions displayed distinct methylation profiles. SMARCB1 loss correlated with increased DNA methylation and DNMT3A/B overexpression. To assess their respective roles in RTs, we used CRISPR-Cas9 to knock out DNMT3A/B in a SMARCB1-inducible RT cell line. DNMT3B loss impaired viability more strongly than DNMT3A. DNMT3B knock-out and SMARCB1 re-expression regulated overlapping gene programs related to development and cell adhesion at methylation and transcriptional levels. We next demonstrated that the cytotoxicity of the DNMT inhibitor decitabine, which impairs RT cell growth in human iPS-derived cerebral organoids, is primarily mediated by DNMT3B. Conclusions: These results show that DNMT3B plays a key role in the cascade of epigenetic effects following SMARCB1 loss and is pivotal in the RT sensitivity to decitabine; our study therefore supports the development of DNMT3B-specific inhibitors for RT.
2026-06-29 | GSE336418 | GEO
Project description:We used microarrays to compare gene expression profilings in various SMARCB1-deficient tumors.
2017-08-13 | GSE94321 | GEO
Project description:Ataxia-telangiectasia mutated (ATM) kinase plays a central role in maintaining genomic integrity. In both humans and mice, ATM deficiency is associated with an increased incidence of lymphoid cancers that are primarily T cell in origin. We demonstrate here that when T cells are removed as targets for lymphomagenesis and as mediators of immune surveillance, ATM-deficient mice exclusively develop early onset IgM+ B cell lymphomas that by histology and gene expression profiling resemble the activated B cell-like (ABC) subset of human diffuse large B cell lymphomas (DLBCL). These ATM-deficient B cell tumors show considerable chromosomal instability and a recurrent genomic amplification of a 4.48 Mb region on chromosome 18 that contains Malt1 and is orthologous to a region similarly amplified in human ABC-DLBCL. Further, the amplification of Malt1 in these lymphomas correlates with their dependence on NF-kB, MALT1, and BCR signaling for survival, paralleling human ABC-DLBCL. This study reveals that ATM protects against development of B cell lymphomas that model human ABC-DLBCL and identifies a role for T cells in preventing the emergence of these tumors.
2015-12-09 | GSE68505 | GEO