Expression data from Sarcoma Tumors expressing the EWSR1-CREB fusions [microarray]
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE168560 | GEO | 2021/08/18
REPOSITORIES: GEO
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Project description:We report RNA-seq for rare 3 rare entities of sarcoma tumors (AFH, CCS and GI-CCS) expressing the EWSR1-CREB1 and EWSR1-ATF1 oncogenic fusion
2021-08-18 | GSE168561 | GEO
Project description:Chimeric proteins resulting from chromosomal translocations play a major role as driver oncogenes in cancer. Among them, fusions between EWSR1 and a set of transcription factors (TFs) generate oncogenes with powerful chromatin regulatory activities, capable of establishing complex gene expression programs. However, specific EWSR1 fusion proteins have been implicated in distinct tumor types, suggesting an enhancement of their functional properties by permissive precursor cells. Here we combined functional epigenomics with nuclear topology mapping to define the epigenetic and 3D connectivity landscape of Clear Cell Sarcoma (CCS), one of the most aggressive forms of human cancer, driven by the EWSR1-ATF1 fusion gene. We find that EWSR1-ATF1 display a distinctive binding pattern that depends on the EWSR1 prion-like domain, and is divergent from wild type ATF1, despite the physical interaction between wt and EWSR1-ATF1 proteins. This cooperativity promotes ATF1 retargeting to new distal sites, leading to chromatin activation and the establishment of a 3D network that controls oncogenic and differentiation signatures shared with primary CCS tumors. Conversely, EWSR1-ATF1 depletion results in a marked reconfiguration of 3D connectivity, including the emergence of a new set of connections controlling neural crest-related developmental programs. Accordingly, interrogation of more than 160,000 single cell expression profiles from the human skin atlas reveals loss of EWSR1-ATF1 expression to induce a more differentiated tumor cell state. Taken together, our study uncovers the cooperativity network of EWSR1-ATF1, delineates the molecular underpinnings of its epigenetic function in CCS, and points to precursor cells along the Schwann cell-melanocytic axis as a candidate origin for these tumors.
2022-03-04 | GSE180183 | GEO
Project description:Chimeric proteins resulting from chromosomal translocations play a major role as driver oncogenes in cancer. Among them, fusions between EWSR1 and a set of transcription factors (TFs) generate oncogenes with powerful chromatin regulatory activities, capable of establishing complex gene expression programs. However, specific EWSR1 fusion proteins have been implicated in distinct tumor types, suggesting an enhancement of their functional properties by permissive precursor cells. Here we combined functional epigenomics with nuclear topology mapping to define the epigenetic and 3D connectivity landscape of Clear Cell Sarcoma (CCS), one of the most aggressive forms of human cancer, driven by the EWSR1-ATF1 fusion gene. We find that EWSR1-ATF1 display a distinctive binding pattern that depends on the EWSR1 prion-like domain, and is divergent from wild type ATF1, despite the physical interaction between wt and EWSR1-ATF1 proteins. This cooperativity promotes ATF1 retargeting to new distal sites, leading to chromatin activation and the establishment of a 3D network that controls oncogenic and differentiation signatures shared with primary CCS tumors. Conversely, EWSR1-ATF1 depletion results in a marked reconfiguration of 3D connectivity, including the emergence of a new set of connections controlling neural crest-related developmental programs. Accordingly, interrogation of more than 160,000 single cell expression profiles from the human skin atlas reveals loss of EWSR1-ATF1 expression to induce a more differentiated tumor cell state. Taken together, our study uncovers the cooperativity network of EWSR1-ATF1, delineates the molecular underpinnings of its epigenetic function in CCS, and points to precursor cells along the Schwann cell-melanocytic axis as a candidate origin for these tumors.
2022-03-04 | GSE180196 | GEO
Project description:Chimeric proteins resulting from chromosomal translocations play a major role as driver oncogenes in cancer. Among them, fusions between EWSR1 and a set of transcription factors (TFs) generate oncogenes with powerful chromatin regulatory activities, capable of establishing complex gene expression programs. However, specific EWSR1 fusion proteins have been implicated in distinct tumor types, suggesting an enhancement of their functional properties by permissive precursor cells. Here we combined functional epigenomics with nuclear topology mapping to define the epigenetic and 3D connectivity landscape of Clear Cell Sarcoma (CCS), one of the most aggressive forms of human cancer, driven by the EWSR1-ATF1 fusion gene. We find that EWSR1-ATF1 display a distinctive binding pattern that depends on the EWSR1 prion-like domain, and is divergent from wild type ATF1, despite the physical interaction between wt and EWSR1-ATF1 proteins. This cooperativity promotes ATF1 retargeting to new distal sites, leading to chromatin activation and the establishment of a 3D network that controls oncogenic and differentiation signatures shared with primary CCS tumors. Conversely, EWSR1-ATF1 depletion results in a marked reconfiguration of 3D connectivity, including the emergence of a new set of connections controlling neural crest-related developmental programs. Accordingly, interrogation of more than 160’000 single cell expression profiles from the human skin atlas reveals loss of EWSR1-ATF1 expression to induce a more differentiated tumor cell state. Taken together, our study uncovers the cooperativity network of EWSR1-ATF1, delineates the molecular underpinnings of its epigenetic function in CCS, and points to precursor cells along the Schwann cell-melanocytic axis as a candidate origin for these tumors.
2022-03-04 | GSE180194 | GEO
Project description:Chimeric proteins resulting from chromosomal translocations play a major role as driver oncogenes in cancer. Among them, fusions between EWSR1 and a set of transcription factors (TFs) generate oncogenes with powerful chromatin regulatory activities, capable of establishing complex gene expression programs. However, specific EWSR1 fusion proteins have been implicated in distinct tumor types, suggesting an enhancement of their functional properties by permissive precursor cells. Here we combined functional epigenomics with nuclear topology mapping to define the epigenetic and 3D connectivity landscape of Clear Cell Sarcoma (CCS), one of the most aggressive forms of human cancer, driven by the EWSR1-ATF1 fusion gene. We find that EWSR1-ATF1 display a distinctive binding pattern that depends on the EWSR1 prion-like domain, and is divergent from wild type ATF1, despite the physical interaction between wt and EWSR1-ATF1 proteins. This cooperativity promotes ATF1 retargeting to new distal sites, leading to chromatin activation and the establishment of a 3D network that controls oncogenic and differentiation signatures shared with primary CCS tumors. Conversely, EWSR1-ATF1 depletion results in a marked reconfiguration of 3D connectivity, including the emergence of a new set of connections controlling neural crest-related developmental programs. Accordingly, interrogation of more than 160,000 single cell expression profiles from the human skin atlas reveals loss of EWSR1-ATF1 expression to induce a more differentiated tumor cell state. Taken together, our study uncovers the cooperativity network of EWSR1-ATF1, delineates the molecular underpinnings of its epigenetic function in CCS, and points to precursor cells along the Schwann cell-melanocytic axis as a candidate origin for these tumors.
2022-03-04 | GSE180187 | GEO
Project description:Clear cell sarcoma (CCS) is a rare soft tissue sarcoma caused by the EWS/ATF1 fusion gene. Here, we established induced pluripotent stem cells (iPSCs) from EWS/ATF1-controllable murine CCS cells harboring sarcoma-associated genetic abnormalities. Sarcoma-iPSC mice develop secondary sarcomas immediately after EWS/ATF1 induction, but only in soft tissue. EWS/ATF1 expression induces oncogene-induced senescence in most cell types in sarcoma-iPSC mice but prevents it in sarcoma cells. We identify Tppp3-expressing cells in peripheral nerves as a cell-of-origin for these sarcomas. We show cell type-specific recruitment of EWS/ATF1 to enhancer regions in CCS cells. Finally, epigenetic silencing at these enhancers induces senescence and inhibits CCS cell growth through altered EWS/ATF1 binding. Together, we propose that distinct responses to premature senescence are the basis for the cell type-specificity of cancer development.
2019-07-18 | GSE77203 | GEO
Project description:Clear cell sarcoma (CCS) is a rare soft tissue sarcoma caused by the EWS/ATF1 fusion gene. Here, we established induced pluripotent stem cells (iPSCs) from EWS/ATF1-controllable murine CCS cells harboring sarcoma-associated genetic abnormalities. Sarcoma-iPSC mice develop secondary sarcomas immediately after EWS/ATF1 induction, but only in soft tissue. EWS/ATF1 expression induces oncogene-induced senescence in most cell types in sarcoma-iPSC mice but prevents it in sarcoma cells. We identify Tppp3-expressing cells in peripheral nerves as a cell-of-origin for these sarcomas. We show cell type-specific recruitment of EWS/ATF1 to enhancer regions in CCS cells. Finally, epigenetic silencing at these enhancers induces senescence and inhibits CCS cell growth through altered EWS/ATF1 binding. Together, we propose that distinct responses to premature senescence are the basis for the cell type-specificity of cancer development.
2019-07-18 | GSE77204 | GEO
Project description:Clear cell sarcoma (CCS) is a rare soft tissue sarcoma caused by the EWS/ATF1 fusion gene. Here, we established induced pluripotent stem cells (iPSCs) from EWS/ATF1-controllable murine CCS cells harboring sarcoma-associated genetic abnormalities. Sarcoma-iPSC mice develop secondary sarcomas immediately after EWS/ATF1 induction, but only in soft tissue. EWS/ATF1 expression induces oncogene-induced senescence in most cell types in sarcoma-iPSC mice but prevents it in sarcoma cells. We identify Tppp3-expressing cells in peripheral nerves as a cell-of-origin for these sarcomas. We show cell type-specific recruitment of EWS/ATF1 to enhancer regions in CCS cells. Finally, epigenetic silencing at these enhancers induces senescence and inhibits CCS cell growth through altered EWS/ATF1 binding. Together, we propose that distinct responses to premature senescence are the basis for the cell type-specificity of cancer development.
2019-08-01 | GSE124873 | GEO
Project description:Expression data from Sarcoma Tumors expressing the EWSR1-CREB fusions
| PRJNA708292 | ENA
Project description:Mice formed tumors either after a TATCre-induced floxed-STOP removal from an EWSR1-ATF1 human cDNA expression vector targeted to the Rosa26 endogenous pseudogene or after an Hprt-Cre-initiated translocation between Ewsr1 and Atf1 genes on chromosomes 11 and 15. From total RNA, libraries were generated using the RiboZero method and sequenced on an Ilumina NovaSeq instrument to permit comparison to each other.
2020-09-30 | GSE158725 | GEO