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| Status |
Public on May 27, 2017 |
| Title |
Large-scale assessment of the gliomasphere model system |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Some aspects of the gene expression-based classification method were robust because the gliomasphere cultures retained their classification over many passages, and IDH1 mutant gliomaspheres were all proneural. While gene expression of a subset of gliomasphere cultures was more like the parent tumor than any other tumor, gliomaspheres did not always harbor the same classification as their parent tumor. Classification was not associated with whether a sphere culture was derived from primary or recurrent GBM or associated with the presence of EGFR amplification or rearrangement. Unsupervised clustering of gliomasphere gene expression distinguished 2 general categories (mesenchymal and nonmesenchymal), while multidimensional scaling distinguished 3 main groups and a fourth minor group. Unbiased approaches revealed that PI3Kinase, protein kinase A, mTOR, ERK, Integrin, and beta-catenin pathways were associated with in vitro measures of proliferation and sphere formation. Associating gene expression with gliomasphere phenotypes and patient outcome, we identified genes not previously associated with GBM: PTGR1, which suppresses proliferation, and EFEMP2 and LGALS8, which promote cell proliferation.
This comprehensive assessment reveals advantages and limitations of using gliomaspheres to model GBM biology, and provides a novel strategy for selecting genes for future study.
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| Overall design |
We used 71 gliomasphere cultures from 68 individuals. Using gene expression-based classification, we performed unsupervised clustering and associated gene expression with gliomasphere phenotypes and patient survival.
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| Contributor(s) |
Laks DR, Crisman TJ, Shih MY, Mottahedeh J, Gao F, Sperry J, Garrett MC, Yong WH, Cloughesy TF, Liau LM, Lai A, Coppola G, Kornblum HI |
| Citation(s) |
27116978 |
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| Submission date |
May 17, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Giovanni Coppola |
| E-mail(s) |
gcoppola@ucla.edu
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| Phone |
310-794-4172
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| Organization name |
UCLA
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| Department |
Psychiatry and Neurology
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| Lab |
Neurogenetics
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| Street address |
1524 Gonda, 695 Charles Young Drive South
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| City |
Los Angeles |
| State/province |
CA |
| ZIP/Postal code |
90095 |
| Country |
USA |
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| Platforms (1) |
| GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
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| Samples (71)
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| Relations |
| BioProject |
PRJNA386943 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE98995_RAW.tar |
342.2 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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