Super-enhancers and efficacy of triptolide in small cell carcinoma of the ovary hypercalcemic type
Small cell carcinoma of the ovary-hypercalcemic type (SCCOHT) is a rare ovarian cancer affecting young females and is driven by the loss of both SWI/SNF ATPases SMARCA4 and SMARCA2. As loss of SWI/SNF alters enhancers, we hypothesized that super-enhancers, which regulate oncogene expression in cance...
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| Hauptverfasser: | , , , , , , , , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
January 7, 2025
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| In: |
iScience
Year: 2025, Jahrgang: 28, Heft: 2, Pages: 1-e6 |
| ISSN: | 2589-0042 |
| DOI: | 10.1016/j.isci.2025.111770 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.isci.2025.111770 Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S258900422500029X 
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| Verfasserangaben: | Jessica D. Lang, William Selleck, Shawn Striker, Nicolle A. Hipschman, Rochelle Kofman, Anthony N. Karnezis, Felix K.F. Kommoss, Friedrich Kommoss, Jae Rim Wendt, Salvatore J. Facista, William P.D. Hendricks, Krystal A. Orlando, Patrick Pirrotte, Elizabeth A. Raupach, Victoria L. Zismann, Yemin Wang, David G. Huntsman, Bernard E. Weissman, and Jeffrey M. Trent |
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| 245 | 1 | 0 | |a Super-enhancers and efficacy of triptolide in small cell carcinoma of the ovary hypercalcemic type |c Jessica D. Lang, William Selleck, Shawn Striker, Nicolle A. Hipschman, Rochelle Kofman, Anthony N. Karnezis, Felix K.F. Kommoss, Friedrich Kommoss, Jae Rim Wendt, Salvatore J. Facista, William P.D. Hendricks, Krystal A. Orlando, Patrick Pirrotte, Elizabeth A. Raupach, Victoria L. Zismann, Yemin Wang, David G. Huntsman, Bernard E. Weissman, and Jeffrey M. Trent |
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| 520 | |a Small cell carcinoma of the ovary-hypercalcemic type (SCCOHT) is a rare ovarian cancer affecting young females and is driven by the loss of both SWI/SNF ATPases SMARCA4 and SMARCA2. As loss of SWI/SNF alters enhancers, we hypothesized that super-enhancers, which regulate oncogene expression in cancer, are disparately impacted by SWI/SNF loss. We discovered differences between SWI/SNF occupancy at enhancers vs. super-enhancers. SCCOHT super-enhancer target genes were enriched in developmental processes, most notably nervous system development. This may further support neuronal cell-of-origin previously proposed. We found high sensitivity of SCCOHT cell lines to triptolide. Triptolide inhibits expression of many super-enhancer-associated genes, including oncogenes. SALL4 expression is decreased by triptolide and is highly expressed in SCCOHT tumors. In patient-derived xenograft models, triptolide and prodrug minnelide effectively inhibit tumor growth. These results reveal unique features of super-enhancers in SCCOHT, which may be one mechanism through which triptolide has high activity in these tumors. | ||
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| 700 | 1 | |a Hipschman, Nicolle A. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Kofman, Rochelle |e VerfasserIn |4 aut | |
| 700 | 1 | |a Karnezis, Anthony N. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Kommoss, Felix |d 1991- |e VerfasserIn |0 (DE-588)1171010427 |0 (DE-627)1040361315 |0 (DE-576)512915164 |4 aut | |
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| 700 | 1 | |a Wendt, Jae Rim |e VerfasserIn |4 aut | |
| 700 | 1 | |a Facista, Salvatore J. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Hendricks, William P. D. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Orlando, Krystal A. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Pirrotte, Patrick |e VerfasserIn |4 aut | |
| 700 | 1 | |a Raupach, Elizabeth A. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Zismann, Victoria L. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Wang, Yemin |e VerfasserIn |4 aut | |
| 700 | 1 | |a Huntsman, David G. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Weissman, Bernard E. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Trent, Jeffrey M. |e VerfasserIn |4 aut | |
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