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

Released on 1 October 2013, last updated on 3 June 2014
Mus musculus
Samples (6)
Array (1)
Protocols (7)
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 
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