Unique features of the transcriptional response to model aneuploidy in human cells

Background: Aneuploidy, a karyotype deviating from multiples of a haploid chromosome set, affects the physiology of eukaryotes. In humans, aneuploidy is linked to pathological defects such as developmental abnormalities, mental retardation or cancer, but the underlying mechanisms remain elusive. There are many different types and origins of aneuploidy, but whether there is a uniform cellular response to aneuploidy in human cells has not been addressed so far. Results: Here we evaluate the transcription profiles of eleven trisomic and tetrasomic cell lines and two cell lines with complex aneuploid karyotypes. We identify a characteristic aneuploidy response pattern defined by upregulation of genes linked to endoplasmic reticulum, Golgi apparatus and lysosomes, and downregulation of DNA replication, transcription as well as ribosomes. Strikingly, complex aneuploidy elicits the same transcriptional changes as trisomy. To uncover the triggers of the response, we compared the profiles with transcription changes in human cells subjected to stress conditions. Interestingly, we found an overlap only with the response to treatment with the autophagy inhibitor bafilomycin A1. Finally, we identified 23 genes whose expression is significantly altered in all aneuploids and which may thus serve as aneuploidy markers. Conclusions: Our analysis shows that despite the variability in chromosome content, aneuploidy triggers uniform transcriptional response in human cells. A common response independent of the type of aneuploidy might be exploited as a novel target for cancer therapy. Moreover, the potential aneuploidy markers identified in our analysis might represent novel biomarkers to assess the malignant potential of a tumor

Consequences of Aneuploidy in Cancer: Transcriptome and Beyond

Cancer cells differ from normal healthy cells in multiple aspects ranging from altered cellular signaling through metabolic changes to aberrant chromosome content, so called aneuploidy. The large-scale changes in copy numbers of chromosomes or large chromosomal regions due to aneuploidy alter significantly the gene expression, as several hundreds of genes are gained or lost. Comparison of quantitative genome, transcriptome and proteome data enables dissection of the molecular causes that underlie the gene expression changes observed in cancer cells and provides a new perspective on the molecular consequences of aneuploidy. Here, we will map to what degree aneuploidy affects the expression of genes located on the affected chromosomes. We will also address the effects of aneuploidy on global gene expression in cancer cells as well as whether and how it may contribute to the physiology of cancer cell

A Procedure for the Construction of the Structure of Fuzzy Neural Networks

A fuzzy neural network is presented where the structure will be generated in the learning algorithm. The system recognizes node regions where new nodes have to be introduced such that the system will be able to use the offered information in the learning examples

Effects of aneuploidy on gene expression: implications for cancer

Unbalanced chromosome content, so-called aneuploidy, is a hallmark of cancer cells. Changes in the copy numbers of chromosomes or large chro- mosomal regions significantly alter the expression of several hundreds of genes that are gained or lost. At the same time, aneuploidy per se affects the transcription of many genes throughout the entire genome, as several pathways are activated or inhibited in response to changes in chromosome copy number. In recent years, a large amount of quantitative genome, tran- scriptome and proteome data has enabled comparison of the changes in gene expression observed in aneuploid cancer cells, as well as in model ane- uploid cells with defined karyotypes. Here, we summarize how aneuploidy shapes gene expression and how it may contribute to the phenotypes of cancer cells