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| Status |
Public on Mar 01, 2020 |
| Title |
A Patient-specific screen identifies Medulloblastoma driver genes in-vivo and in human organoids |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by genome tiling array
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| Summary |
Group3 Medulloblastoma is a highly malignant pediatric brain tumor and despite patients harboring different genetic alterations they are treated with similar therapies. Here, we perform an in-vivo Patient-Specific screen and we identify Otx2 and c-Myc as strong inducers of Group3 Medulloblastoma. We demonstrate that the chromatin modifier Smarca4, also mutated in human patients, is able to reduce Otx2/c-Myc tumorigenic activity in-vivo.
Furthermore, Otx2/c-Myc co-overexpression in human cerebellar organoids generates Medulloblastoma-like organoids that induce brain cancer in mice with a DNA methylation signature similar to human Group3 MB. Finally, inhibition of histone methyltransferases reduces Otx2/c-Myc tumorigenesis in ex-vivo culture and in human cerebellar organoids. Therefore, understanding the role of different altered genes in Medulloblastoma patients will be of great importance to develop new personalized therapies.
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| Overall design |
To classify new Group3 Medulloblastoma (MB) derived from human organoids, we analyzed the global DNA methylation profile of Otx2+c-Myc (OM) injected organoids and compared them with those derived from 36 MB patients, diagnosed and treated at the Ospedale Pediatrico Bambino Gesù (OPBG Rome).
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| Contributor(s) |
Tiberi L, Ballabio C, Anderle M, Gianesello M, Miele E, Lago C, Cardano M, Aiello G, Piazza S, Caron D, Gianno F, Ciolfi A, Pedace L, Matronuzzi A, Tartaglia M, Locatelli F, Ferretti E, Giangaspero F |
| Citation(s) |
31996670 |
| Submission date |
Mar 13, 2019 |
| Last update date |
Jun 01, 2020 |
| Contact name |
Evelina Miele |
| E-mail(s) |
evelina.miele@opbg.net
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| Organization name |
Ospedale Pediatrico Bambino Gesù
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| Department |
Oncoematologia
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| Street address |
Piazza di Sant'Onofrio 4
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| City |
Rome |
| ZIP/Postal code |
00165 |
| Country |
Italy |
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| Platforms (1) |
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| Samples (45)
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| Relations |
| BioProject |
PRJNA526827 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE128218_RAW.tar |
794.4 Mb |
(http)(custom) |
TAR (of IDAT) |
| GSE128218_p-values.txt.gz |
8.4 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
| Processed data are available on Series record |
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