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Modeling medulloblastoma in vivo and with human cerebellar organoids.

Nat Commun. 2020; 
Ballabio C, Anderle M, Gianesello M, Lago C, Miele E, Cardano M, Aiello G, Piazza S, Caron D, Gianno F,, Ciolfi A, Pedace L, Mastronuzzi A, Tartaglia M, Locatelli F,, Ferretti E, Giangaspero F,, Tiberi L.
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ORF cDNA Clones/MolecularCloud The pSpCas9(BB)-2A-GFP (PX458) plasmids bearing three different sgRNAs targeting murine Smarca4 gene were purchased from GenScript. Get A Quote

摘要

Medulloblastoma (MB) is the most common malignant brain tumor in children and among the subtypes, Group 3 MB has the worst outcome. Here, we perform an in vivo, patient-specific screen leading to the identification of Otx2 and c-MYC as strong Group 3 MB inducers. We validated our findings in human cerebellar organoids where Otx2/c-MYC give rise to MB-like organoids harboring a DNA methylation signature that clusters with human Group 3 tumors. Furthermore, we show that SMARCA4 is able to reduce Otx2/c-MYC tumorigenic activity in vivo and in human cerebellar organoids while SMARCA4 T910M, a mutant form found in human MB patients, inhibits the wild-type protein function. Finally, treatment with Tazemetostat, a ... More

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