E-GEOD-49894 - A transcriptional and metabolic signature of primary aneuploidy is present in chromosomally-unstable cancer cells and informs clinical prognosis

Status
Released on 1 October 2013, last updated on 3 June 2014
Organism
Mus musculus
Samples (6)
Array (1)
Protocols (7)
Description
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. 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
Experiment type
transcription profiling by array 
Contacts
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-49894.idf.txt
Sample and data relationshipE-GEOD-49894.sdrf.txt
Raw data (1)E-GEOD-49894.raw.1.zip
Processed data (1)E-GEOD-49894.processed.1.zip
Array designA-AFFY-36.adf.txt
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