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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Mar 15, 2007 |
| Title |
Genetic alterations in mouse medulloblastomas and generation of tumors from cerebellar grunule neuron precursors |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Mice lacking p53 and one or two alleles of the cyclin D-dependent kinase inhibitor p18Ink4c are prone to medulloblastoma development. The tumor frequency is increased by exposing postnatal animals to ionizing radiation at a time when their cerebella are developing. In irradiated mice engineered to express a floxed p53 allele and a Nestin-Cre transgene, tumor development can be restricted to the brain. Analysis of these animals indicated that inactivation of one or both Ink4c alleles did not affect the time of medulloblastoma onset but increased tumor invasiveness. All such tumors exhibited complete loss of function of the Patched 1 (Ptc1) gene encoding the receptor for sonic hedgehog, and many exhibited other recurrent genetic alterations, including trisomy of chromosome 6, amplification of N-Myc, modest increases in copy number of the Ccnd1 gene encoding cyclin D1, and other complex chromosomal rearrangements. In contrast, medulloblastomas arising in Ptc1+/- mice lacking one or both Ink4c alleles retained p53 function and exhibited only limited genomic instability. Nonetheless, complete inactivation of the wild type Ptc1 allele was a universal event, and trisomy of chromosome 6 was again frequent. The enforced expression of N-Myc or cyclin D1 in primary cerebellar granule neuron precursors isolated from Ink4c-/-, p53-/- mice enabled the cells to initiate medulloblastomas when injected back into the brains of immunocompromised recipient animals. These engineered tumors exhibited gene expression profiles indistinguishable from those of medulloblastomas that arose spontaneously. These results underscore the functional interplay between a network of specific genes that recurrently contribute to medulloblastoma formation.
Keywords: disease state analysis
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| Overall design |
5 samples, 2 states
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| Contributor(s) |
Zindy F, Uziel T, Ayrault O, Calabrese C, Valentine M, Rehg JE, Gilbertson RJ, Sherr CJ, Roussel MF |
| Citation(s) |
17363588 |
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| Submission date |
Dec 06, 2006 |
| Last update date |
Jan 08, 2019 |
| Contact name |
Chunxu Qu |
| E-mail(s) |
[email protected]
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| Phone |
9015952433
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| Organization name |
St Jude Children's Research Institute
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| Department |
Pathology
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| Lab |
Mullighan
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| Street address |
262 Danny Thomas Pl
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| City |
Memphis |
| State/province |
TN |
| ZIP/Postal code |
38105 |
| Country |
USA |
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| Platforms (2) |
| GPL339 |
[MOE430A] Affymetrix Mouse Expression 430A Array |
| GPL340 |
[MOE430B] Affymetrix Mouse Expression 430B Array |
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| Samples (10)
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| GSM148573 |
granule neuron precursors, biological replicate 1; array A |
| GSM148574 |
granule neuron precursors, biological replicate 2; array A |
| GSM148575 |
granule neuron precursors, biological replicate 3; array A |
| GSM148576 |
granule neuron precursors infected with retroviruses that express N-myc; array A |
| GSM148577 |
granule neuron precursors infected with retroviruses that express Cyclin D1; array A |
| GSM148578 |
granule neuron precursors, biological replicate 1; array B |
| GSM148579 |
granule neuron precursors, biological replicate 2; array B |
| GSM148580 |
granule neuron precursors, biological replicate 3; array B |
| GSM148581 |
granule neuron precursors infected with retroviruses that express N-myc; array B |
| GSM148582 |
granule neuron precursors infected with retroviruses that express Cyclin D1; array B |
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| Relations |
| BioProject |
PRJNA98695 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE6463_RAW.tar |
19.4 Mb |
(http)(custom) |
TAR (of CEL) |
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