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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 |
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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 |