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| Status |
Public on Jun 01, 2018 |
| Title |
Rictor/mTORC2 signaling has opposing functions in adult glioma and childhood SHH medulloblastoma |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Primary glioblastoma, representing over 90% of adult glioblastoma, develop rapidly without preexisting lower-grade glioma. We have generated a mouse model of primary glioblastoma driven by a single p53 mutation. These p53-mutant gliomas lose the syntenic region of human chromosome 10q, which is mapped to mouse chr19 and chr7. Loss of mouse chr19, containing Pten, activates PI3K/Akt signaling.
Rictor/mTORC2 deletion inhibits Akt signaling, causing a significant delay in p53-mutant driven glioma formation. Unexpectedly, Rictor/mTORC2 loss promotes p53-mutant driven medulloblastomas with unique features of pediatric SHH medulloblastoma. Mechanistically, Rictor/mTORC2 loss inhibits the generation of glioma precursor cells from neural stem/progenitor cells in the adult brain, while causing a delay in differentiation of granule cell precursors in the developing brain, a cell-of-origin of SHH medulloblastoma.
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| Overall design |
In this study we generate mouse models with (1) p53 loss (2) p53 loss combined with gemline Nf1 mutation (3) a conditional cis-p53/Nf1 mutation. We profiled the resultant tumors as well as normal forebrain and cerebellum as controls.
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| Contributor(s) |
Zhu Y |
| Citation(s) |
29996106 |
| |
| Submission date |
Mar 04, 2016 |
| Last update date |
Aug 31, 2018 |
| Contact name |
Yuan Zhu |
| E-mail(s) |
YZhu@childrensnational.org
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| Organization name |
Children's National Medical Center
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| Street address |
111 Michigan Ave NW
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| City |
Washington DC |
| State/province |
DC |
| ZIP/Postal code |
20010 |
| Country |
USA |
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| Platforms (1) |
| GPL9523 |
[Mouse430_2] Affymetrix GeneChip Mouse Genome 430 2.0 Array [Alternative CDF: affy9618alt] |
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| Samples (32)
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| Relations |
| BioProject |
PRJNA314322 |
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