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| Home > Publications database > YAP1 subgroup supratentorial ependymoma requires TEAD and nuclear factor I-mediated transcriptional programmes for tumorigenesis. > print |
| 001 | 144769 | ||
| 005 | 20240229112637.0 | ||
| 024 | 7 | _ | |a 10.1038/s41467-019-11884-5 |2 doi |
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| 100 | 1 | _ | |a Pajtler, Kristian |0 P:(DE-He78)a7c1bbac024fa232d9c6b78443328d9d |b 0 |e First author |
| 245 | _ | _ | |a YAP1 subgroup supratentorial ependymoma requires TEAD and nuclear factor I-mediated transcriptional programmes for tumorigenesis. |
| 260 | _ | _ | |a [London] |c 2019 |b Nature Publishing Group UK |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1631542257_4439 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
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| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 520 | _ | _ | |a YAP1 fusion-positive supratentorial ependymomas predominantly occur in infants, but the molecular mechanisms of oncogenesis are unknown. Here we show YAP1-MAMLD1 fusions are sufficient to drive malignant transformation in mice, and the resulting tumors share histo-molecular characteristics of human ependymomas. Nuclear localization of YAP1-MAMLD1 protein is mediated by MAMLD1 and independent of YAP1-Ser127 phosphorylation. Chromatin immunoprecipitation-sequencing analyses of human YAP1-MAMLD1-positive ependymoma reveal enrichment of NFI and TEAD transcription factor binding site motifs in YAP1-bound regulatory elements, suggesting a role for these transcription factors in YAP1-MAMLD1-driven tumorigenesis. Mutation of the TEAD binding site in the YAP1 fusion or repression of NFI targets prevents tumor induction in mice. Together, these results demonstrate that the YAP1-MAMLD1 fusion functions as an oncogenic driver of ependymoma through recruitment of TEADs and NFIs, indicating a rationale for preclinical studies to block the interaction between YAP1 fusions and NFI and TEAD transcription factors. |
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| 700 | 1 | _ | |a Silva, Patricia B G |0 P:(DE-HGF)0 |b 3 |e First author |
| 700 | 1 | _ | |a Vouri, Mikaella |0 P:(DE-He78)7a849fbc18c1307faf2b3a4f84a62500 |b 4 |
| 700 | 1 | _ | |a Zhang, Lei |b 5 |
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| 700 | 1 | _ | |a Gulley, Melissa |b 8 |
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| 700 | 1 | _ | |a Mack, Norman |0 P:(DE-He78)e73a0a4fab40344d89d693cbe1df3109 |b 11 |
| 700 | 1 | _ | |a Imamura Kawasawa, Yuka |b 12 |
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| 700 | 1 | _ | |a Andreiuolo, Felipe |b 15 |
| 700 | 1 | _ | |a Holland, Eric |0 0000-0002-3792-7120 |b 16 |
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| 700 | 1 | _ | |a Bunt, Jens |0 0000-0003-0397-2019 |b 22 |
| 700 | 1 | _ | |a Richards, Linda J |0 0000-0002-7590-7390 |b 23 |
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| 700 | 1 | _ | |a Kool, Marcel |0 P:(DE-He78)4c28e2aade5f44d8eca9dd8e97638ec8 |b 30 |
| 700 | 1 | _ | |a Li, Wei |b 31 |
| 700 | 1 | _ | |a Kawauchi, Daisuke |0 P:(DE-He78)0ac2bd1a9fb1823a351ee4434d80808b |b 32 |e Last author |
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