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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Oct 01, 2013 |
| Title |
A transcriptional and metabolic signature of primary aneuploidy is present in chromosomally-unstable cancer cells and informs clinical prognosis |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
In all primary cells analyzed to date, aneuploidy is associated with poor proliferation. Yet, how abnormal karyotypes affect cancer – a disease characterized by both aneuploidy and heightened proliferative capacity – is largely unknown. Here, I demonstrate that the transcriptional alterations caused by aneuploidy in primary cells are also present in chromosomally-unstable cancer cell lines, but are not common to all aneuploid cancers. Moreover, chromosomally-unstable cancer lines display increased glycolytic and TCA-cycle flux, as is also observed in primary aneuploid cells. The biological response to aneuploidy is associated with cellular stress and slow proliferation, and a 70-gene signature derived from primary aneuploid cells is a strong predictor of increased survival in several cancers. Inversely, a transcriptional signature derived from clonal aneuploidy in tumors correlates with high mitotic activity and poor prognosis. I speculate that there are two types of aneuploidy in cancer: clonal aneuploidy, which is selected during tumor evolution and is associated with robust growth, and sub-clonal aneuploidy, which is caused by chromosomal instability (CIN) and more closely resembles the stressed state of primary aneuploid cells. Nonetheless, CIN is not benign: a subset of genes upregulated in high-CIN cancers predict aggressive disease in human patients in a proliferation-independent manner.
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| Overall design |
The mRNAs from 3 different mouse embryo fibroblast (MEF) lines that are chromosomally stable were compared with mRNAs from 3 different MEF lines that were chromosomally unstable due to mutations in either BUBR1 or CDC20
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| Contributor(s) |
Sheltzer J |
| Citation(s) |
24041940 |
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| Submission date |
Aug 14, 2013 |
| Last update date |
May 04, 2018 |
| Contact name |
Charles Arthur Whittaker |
| E-mail(s) |
charliew@mit.edu
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| Organization name |
Koch Institute
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| Street address |
77 Mass Ave 76-189
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| City |
Cambridge |
| State/province |
MA |
| ZIP/Postal code |
02152 |
| Country |
USA |
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| Platforms (1) |
| GPL8321 |
[Mouse430A_2] Affymetrix Mouse Genome 430A 2.0 Array |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA215259 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE49894_RAW.tar |
13.1 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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