| Online-Ressource |
Verfasst von: | Solé Ferré, Anna [VerfasserIn]  |
| Grossetête, Sandrine [VerfasserIn]  |
| Heintzé, Maxime [VerfasserIn]  |
| Babin, Loelia [VerfasserIn]  |
| Zaïdi, Sakina [VerfasserIn]  |
| Revy, Patrick [VerfasserIn]  |
| Renouf, Benjamin [VerfasserIn]  |
| Cian, Anne De [VerfasserIn]  |
| Giovannangeli, Carine [VerfasserIn]  |
| Pierre-Eugène, Cécile [VerfasserIn]  |
| Janoueix-Lerosey, Isabelle [VerfasserIn]  |
| Couronné, Lucile [VerfasserIn]  |
| Kaltenbach, Sophie [VerfasserIn]  |
| Tomishima, Mark [VerfasserIn]  |
| Jasin, Maria [VerfasserIn]  |
| Grünewald, Thomas G. P. [VerfasserIn]  |
| Delattre, Olivier [VerfasserIn]  |
| Surdez, Didier [VerfasserIn]  |
| Brunet, Erika [VerfasserIn]  |
Titel: | Unraveling Ewing sarcoma tumorigenesis originating from patient-derived mesenchymal stem cells |
Verf.angabe: | Anna Sole, Sandrine Grossetête, Maxime Heintzé, Loelia Babin, Sakina Zaïdi, Patrick Revy, Benjamin Renouf, Anne De Cian, Carine Giovannangeli, Cécile Pierre-Eugène, Isabelle Janoueix-Lerosey, Lucile Couronné, Sophie Kaltenbach, Mark Tomishima, Maria Jasin, Thomas G.P. Grünewald, Olivier Delattre, Didier Surdez, and Erika Brunet |
E-Jahr: | 2021 |
Jahr: | August 2, 2021 |
Umfang: | 13 S. |
Fussnoten: | Gesehen am 25.11.2021 |
Titel Quelle: | Enthalten in: Cancer research |
Ort Quelle: | Philadelphia, Pa. : AACR, 1916 |
Jahr Quelle: | 2021 |
Band/Heft Quelle: | 81(2021), 19, Seite 4994-5006 |
ISSN Quelle: | 1538-7445 |
Abstract: | Ewing sarcoma is characterized by pathognomonic translocations, most frequently fusing EWSR1 with FLI1. An estimated 30% of Ewing sarcoma tumors also display genetic alterations in STAG2, TP53, or CDKN2A (SPC). Numerous attempts to develop relevant Ewing sarcoma models from primary human cells have been unsuccessful in faithfully recapitulating the phenotypic, transcriptomic, and epigenetic features of Ewing sarcoma. In this study, by engineering the t(11;22)(q24;q12) translocation together with a combination of SPC mutations, we generated a wide collection of immortalized cells (EWIma cells) tolerating EWSR1-FLI1 expression from primary mesenchymal stem cells (MSC) derived from a patient with Ewing sarcoma. Within this model, SPC alterations strongly favored Ewing sarcoma oncogenicity. Xenograft experiments with independent EWIma cells induced tumors and metastases in mice, which displayed bona fide features of Ewing sarcoma. EWIma cells presented balanced but also more complex translocation profiles mimicking chromoplexy, which is frequently observed in Ewing sarcoma and other cancers. Collectively, these results demonstrate that bone marrow-derived MSCs are a source of origin for Ewing sarcoma and also provide original experimental models to investigate Ewing sarcomagenesis. - Significance: These findings demonstrate that Ewing sarcoma can originate from human bone-marrow-derived mesenchymal stem cells and that recurrent mutations support EWSR1-FLI1 translocation-mediated transformation. |
DOI: | doi:10.1158/0008-5472.CAN-20-3837 |
URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext: https://doi.org/10.1158/0008-5472.CAN-20-3837 |
| Volltext: https://cancerres.aacrjournals.org/content/81/19/4994 |
| DOI: https://doi.org/10.1158/0008-5472.CAN-20-3837 |
Datenträger: | Online-Ressource |
Sprache: | eng |
K10plus-PPN: | 1779064950 |
Verknüpfungen: | → Zeitschrift |
Unraveling Ewing sarcoma tumorigenesis originating from patient-derived mesenchymal stem cells / Solé Ferré, Anna [VerfasserIn]; August 2, 2021 (Online-Ressource)