Gene expression profiling of aneuploid IMR90 cells induced by Rb, DNMT1 and MAD2 depletion

Segregation errors of chromosomes into daughter cells lead to aneuploidy that is considered a major feature of solid tumors. How diploid cells face chromosome mal-segregation and the mechanisms driving aneuploidy tolerance in tumor cells are not yet completely defined. Thus, an important goal in cancer genetics is to identify gene networks leading to aneuploidy as well involved in its tolerance. To this aim we induced aneuploidy in IMR90 human primary cells and analyzed their gene expression profiles by DNA microarrays. Bioinformatics analysis revealed the presence of shared differentially expressed genes, up or down regulated in IMR90 cells after depletion of pRb, DNMT1 and MAD2 all inducing aneuploidy. Normalized data were also analyzed with the Gene Set Enrichment Analysis (GSEA) software to detect deregulated gene-sets associated with the aneuploidy phenotype. GSEA analysis suggested the existence of shared gene-sets/pathways characterizing aneuploidy cells that might be exploited for novel therapeutic approaches in cancer To search for a molecular signature shared by different IMR-90 aneuploid cell populations generated by depletion of DNMT1, MAD2 and pRb we performed transcriptome analysis to compare expression profiles between IMR-90 cells transfected with siRNA to DNMT1, MAD2 and pRb genes and those transfected with a negative control.