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| 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
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| 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.
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| 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.
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| 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 |
Mar 25, 2019 |
| Contact name |
Chunxu Qu |
| E-mail(s) |
chunxu.qu@stjude.org
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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 (4)
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| 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) |
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| 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 |
| GSM566348 |
RNA, tumor from Pten; p53 double knockout mouse, mouse 278, male |
| GSM566349 |
RNA, tumor2 from Pten; p53 double knockout mouse, mouse 278, male |
| GSM566350 |
RNA, tumor from Pten; p53 double knockout mouse, mouse 340, male |
| GSM566351 |
RNA, tumor2 from Pten; p53 double knockout mouse, mouse 340, male |
| GSM566352 |
RNA, tumor from Pten; p53 double knockout mouse, mouse 404, male |
| GSM566353 |
RNA, tumor from Pten; p53 double knockout mouse, mouse 500, female |
| GSM566354 |
RNA, tumor from Pten; p53 double knockout mouse, mouse 515, male |
| GSM566355 |
RNA, tumor from Pten; p53 double knockout mouse, mouse 554, female |
| GSM566356 |
RNA, tumor from Pten; p53 double knockout mouse, mouse 557, male |
| GSM566357 |
RNA, tumor from Pten; p53 double knockout mouse, mouse 560, female |
| GSM566358 |
RNA, tumor from Pten; p53 double knockout mouse, mouse 658, female |
| GSM566359 |
RNA, tumor from Pten; p53 double knockout mouse, mouse 661, female |
| GSM566360 |
RNA, tumor from Pten; p53 double knockout mouse, mouse 898, female |
| GSM566361 |
RNA, tumor from Pten; p53 double knockout mouse, mouse 900, male |
| GSM566362 |
RNA, tumor from Pten; p53 double knockout mouse, mouse 903, male |
| GSM566363 |
RNA, tumor from Pten; p53 double knockout mouse, mouse 1031, female |
| GSM566364 |
RNA, tumor from Pten; p53 double knockout mouse, mouse 1256, male |
| GSM566365 |
RNA, tumor from Pten; p53 double knockout mouse, mouse 1257, male |
| GSM566366 |
RNA, tumor from Pten; p53 double knockout mouse, mouse 1381, male |
| GSM566367 |
RNA, tumor from Pten; p53 double knockout mouse, mouse 1528, male |
| GSM566405 |
RNA, tumor from Pten; p53; Rb1 triple knockout mouse, mouse 491, male |
| GSM566406 |
RNA, tumor2 from Pten; p53; Rb1 triple knockout mouse, mouse 609, female |
| GSM566407 |
RNA, tumor from Pten; p53; Rb1 triple knockout mouse, mouse 615, male |
| GSM566408 |
RNA, tumor from Pten; p53; Rb1 triple knockout mouse, mouse 670, male |
| GSM566409 |
RNA, tumor from Pten; p53; Rb1 triple knockout mouse, mouse 672, male |
| GSM566410 |
RNA, tumor from Pten; p53; Rb1 triple knockout mouse, mouse 1294, female |
| GSM566411 |
RNA, tumor from Pten; p53; Rb1 triple knockout mouse, mouse 1296, male |
| GSM566412 |
RNA, tumor from Pten; p53; Rb1 triple knockout mouse, mouse 1346, female |
| GSM566413 |
RNA, tumor from Pten; p53; Rb1 triple knockout mouse, mouse 1623, female |
| GSM566414 |
RNA, tumor from Pten; p53; Rb1 triple knockout mouse, mouse 1867, female |
| GSM566415 |
RNA, tumor from Pten; p53; Rb1 triple knockout mouse, mouse 2586, male |
| GSM566416 |
RNA, tumor from Pten; p53; Rb1 triple knockout mouse, mouse 2620, female |
| GSM566417 |
RNA, tumor from Pten; p53; Rb1 triple knockout mouse, mouse 2591, male |
| GSM566418 |
RNA, tumor from Pten; p53; Rb1 triple knockout mouse, mouse 2862, female |
| GSM566499 |
DNA of mouse 440 brain tumor, Female, 119 days |
| GSM566680 |
DNA of mouse 440 brain tumor anterior cortex, Female, 119 days |
| GSM566681 |
DNA of mouse 491 brain tumor cranial nerve, Male, 190 days |
| GSM566682 |
DNA of mouse 609 brain tumor cranial nerve, Female, 158 days |
| GSM566683 |
DNA of mouse 609 brain tumor Olf Bulb, Female, 158 days |
| GSM566700 |
DNA of mouse 615 brain tumor right cortex, Male, 114 days |
| GSM566701 |
DNA of mouse 670 brain tumor cortex, Male, 182 days |
| GSM566702 |
DNA of mouse 672 brain tumor cortex, Male, 187 days |
| GSM566703 |
DNA of mouse 736 brain tumor cortex, Female, 176 days |
| GSM566708 |
DNA of mouse 1296 brain tumor corpus callosum, Male, 170 days |
| GSM566709 |
DNA of mouse 1314 brain tumor right cortex, Female, 179 days |
| GSM566710 |
DNA of mouse 1346 brain tumor cortex, Female, 171 days |
| GSM566711 |
DNA of mouse 1623 brain tumor ventricle, Female, 158 days |
| GSM566712 |
DNA of mouse 1657 brain tumor left cortex, Female, 126 days |
| GSM566713 |
DNA of mouse 1867 brain tumor left ventricle, Female, 144 days |
| GSM566714 |
DNA of mouse 2586 brain tumor ventricle, Male, 101 days |
| GSM566715 |
DNA of mouse 2588 brain tumor hypothalamus, Male, 184 days |
| GSM566740 |
DNA of mouse 2591 brain tumor right cortex, Male, 225 days |
| GSM566741 |
DNA of mouse 2620 brain tumor left cranial nerve, Female, 155 days |
| GSM566742 |
DNA of mouse 2620 brain tumor right cranial nerve, Female, 155 days |
| GSM566743 |
DNA of mouse 2862 brain tumor cortex, Female, 167 days |
| GSM566898 |
DNA of mouse 229 brain tumor right ventricle, Female, 173 days |
| GSM566899 |
DNA of mouse 237 brain tumor corpus callosum, Female, 212 days |
| GSM566900 |
DNA of mouse 250 brain tumor2 frontal lobe, Male, 211 days |
| GSM566901 |
DNA of mouse 250 brain tumor ventricle, Male, 211 days |
| GSM566902 |
DNA of mouse 255 brain tumor cortex, Female, 218 days |
| GSM566903 |
DNA of mouse 270 brain tumor right cortex, Male, 224 days |
| GSM566905 |
DNA of mouse 272 brain tumor2 diffuse, Male, 318 days |
| GSM566906 |
DNA of mouse 274 brain tumor diffuse, Male, 254 days |
| GSM566907 |
DNA of mouse 278 brain tumor2 basal ganglia, Male, 275 days |
| GSM566908 |
DNA of mouse 278 brain tumor cortex, Male, 275 days |
| GSM566909 |
DNA of mouse 287 brain tumor basal ganglia, Female, 209 days |
| GSM566910 |
DNA of mouse 291 brain tumor corpus callosum, Female, 193 days |
| GSM566911 |
DNA of mouse 295 brain tumor ventricle, Male, 241 days |
| GSM566912 |
DNA of mouse 340 brain tumor left CN V, Male, 274 days |
| GSM566913 |
DNA of mouse 340 brain tumor2 basal ganglia, Male, 274 days |
| GSM566914 |
DNA of mouse 343 brain tumor corpus callosum, Male, 205 days |
| GSM566915 |
DNA of mouse 359 brain tumor ventricle, Female, 394 days |
| GSM566916 |
DNA of mouse 404 brain tumor right CN V, Male, 285 days |
| GSM566917 |
DNA of mouse 458 brain tumor internal capsule, Male, 212 days |
| GSM566918 |
DNA of mouse 500 brain tumor basal ganglia, Female, 193 days |
| GSM566919 |
DNA of mouse 515 brain tumor right CN V, Male, 318 days |
| GSM566922 |
DNA of mouse 554 brain tumor right hemisphere, Female, 187 days |
| GSM566923 |
DNA of mouse 555 brain tumor1 spinal cord, Male, 358 days |
| GSM566924 |
DNA of mouse 555 brain tumor2 basal ganglia, Male, 358 days |
| GSM566925 |
DNA of mouse 557 brain tumor ventricle, Male, 244 days |
| GSM566926 |
DNA of mouse 559 brain tumor right hemisphere, Male, 260 days |
| GSM566927 |
DNA of mouse 560 brain tumor right hemisphere, Female, 182 days |
| GSM566928 |
DNA of mouse 658 brain tumor right CN V, Female, 263 days |
| GSM566929 |
DNA of mouse 660 brain tumor basal ganglia, Female, 263 days |
| GSM566930 |
DNA of mouse 661 brain tumor basal ganglia, Female, 155 days |
| GSM566931 |
DNA of mouse 706 brain tumor Dentate gyrus, Male, 250 days |
| GSM566933 |
DNA of mouse 816 brain tumor right olf bulb, Male, 344 days |
| GSM566935 |
DNA of mouse 896 brain tumor2 left cortex, Female, 221 days |
| GSM566936 |
DNA of mouse 896 brain tumor3 septum, Female, 221 days |
| GSM566937 |
DNA of mouse 898 brain tumor spinal cord, Female, 218 days |
| GSM566938 |
DNA of mouse 900 brain tumor cerebellum, Male, 274 days |
| GSM566939 |
DNA of mouse 902 brain tumor left CN V, hypothalamus, Male, 231 days |
| GSM566940 |
DNA of mouse 903 brain tumor right CN V, Male, 235 days |
| GSM566941 |
DNA of mouse 976 brain tumor right hemisphere, Female, 201 days |
| GSM566942 |
DNA of mouse 1031 brain tumor left hemisphere, Female, 196 days |
| GSM566943 |
DNA of mouse 1205 brain tumor corpus callosum, Female, 208 days |
| GSM566944 |
DNA of mouse 1213 brain tumor subventricular zone, Female, 177 days |
| GSM566945 |
DNA of mouse 1245 brain tumor anterior cortex, Male, 230 days |
| GSM566946 |
DNA of mouse 1252 brain tumor cerebellum, Male, 107 days |
| GSM566947 |
DNA of mouse 1254 brain tumor cortex, Male, 247 days |
| GSM566948 |
DNA of mouse 1256 brain tumor left midbrain, Male, 266 days |
| GSM566949 |
DNA of mouse 1257 brain tumor right hemisphere, Male, 162 days |
| GSM566950 |
DNA of mouse 1381 brain tumor right hemisphere, Male, 236 days |
| GSM566951 |
DNA of mouse 1384 brain tumor spinal cord, Male, 179 days |
| GSM566952 |
DNA of mouse 1528 brain tumor anterior cortex, Male, 263 days |
| GSM566953 |
DNA of mouse 2091 brain tumor corpus callosum, Female, 157 days |
| GSM648500 |
mRNA of BSG002T, brainstem low-grade gloma |
| GSM648501 |
mRNA of BSG903T, brainstem low-grade gloma |
| GSM648502 |
mRNA of BSG036T, brainstem low-grade gloma |
| GSM648503 |
mRNA of DLL001T, brainstem low-grade gloma |
| GSM648504 |
mRNA of DLL002T, brainstem low-grade gloma |
| GSM648505 |
mRNA of DLL003T, brainstem low-grade gloma |
| GSM648506 |
mRNA of BKP001, normal pediatric brainstem |
| GSM648507 |
mRNA of BKP002, normal pediatric brainstem |
| GSM648523 |
RNA, tumor from Pten; p53 double knockout mouse, mouse 902, male |
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| Relations |
| BioProject |
PRJNA127619 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE22927_RAW.tar |
1.8 Gb |
(http)(custom) |
TAR (of CEL, GPR, TXT) |
| Processed data included within Sample table |
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