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Series GSE22927 Query DataSets for GSE22927
Status Public on Mar 23, 2011
Title Hierarchical synergy of Pten, p53 and Rb pathways in high-grade astrocytoma induced in adult brain
Organisms Homo sapiens; Mus musculus
Experiment type Expression profiling by array
Genome variation profiling by genome tiling array
Summary Mutations in the PTEN, TP53 and RB1 pathways are obligate events in the pathogenesis of human glioblastomas, the highest grade of astrocytoma. To investigate synergy between these tumor suppressors in mice, we induced various combinations of compound deletions conditionally in astrocytes and neural precursors in the mature brain. The resulting highly penetrant astrocytomas showed a spectrum of histopathological variation reminiscent of human tumors, and ranged from grade III to grade IV (glioblastoma). Secondary somatic mutations varied depending on the combination of initiating deletions and were relevant to human disease. Receptor tyrosine kinase amplifications were frequent in tumors initiated by combined conditional deletion of Pten and Tp53, but not when Rb, Pten and Tp53 were simultaneously deleted. Multiple mutations within PI3K and Rb pathways were acquired, however, Mapk activation was not consistently detected in astrocytomas. Gene expression profiling revealed striking similarities to previously described human astrocytoma subclasses. A subset of astrocytomas initiated outside of proliferative niches in the adult brain.
 
Overall design Gene expression of 8 human brain samples including 2 normal brainstem and 6 brainstem low-grade gliomas were profiled using HG-U133 plus 2 arrays. Gene expression of 38 mouse tumor samples, including 24 Pten;p53 double knockout and 14 Pten;p53;Rb1 triple knockout, were profiled using Affymetrix Mouse Genome 430 v2 arrays. Copy number changes of 51 double knockout tumor samples were analysed using Roswell Park Cancer Institute 6.5k BAC arrays. Copy number changes of 21 triple knockout tumor samples were analysed using Agilent mouse genome CGH mocirarray 244A.
 
Contributor(s) Chow LM, Endersby R, Zhu X, Rankin S, Qu C, Zhang J, Ellison DW, Baker SJ
Citation(s) 21397855
Submission date Jul 13, 2010
Last update date Feb 11, 2019
Contact name Chunxu Qu
E-mail chunxu.qu@stjude.org
Phone 9015955110
Organization name St Jude Children's Research Institute
Street address 332 N. Lauderdale St
City Memphis
State/province TN
ZIP/Postal code 38105
Country USA
 
Platforms (4)
GPL570 [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array
GPL1261 [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array
GPL4092 Agilent-014695 Mouse Genome CGH Microarray 244A (G4415A) (Feature Number version)
Samples (118)
GSM566195 RNA, tumor from Pten; p53 double knockout mouse, mouse 250, male
GSM566346 RNA, tumor from Pten; p53 double knockout mouse, mouse 274, male
GSM566347 RNA, tumor from Pten; p53 double knockout mouse, mouse 287, female
Relations
BioProject PRJNA127619

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE22927_RAW.tar 1.8 Gb (http)(custom) TAR (of CEL, GPR, TXT)
Raw data provided as supplementary file
Processed data included within Sample table

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