Identification of pathways involved in aneuploidy onset and its tolerance using a DNA microarray approach

Genomic instability is a hallmark of the majority of human tumors explaining the heterogeneity shown by tumor cells. This phenomenon is often associated with chromosomal instability (CIN) and aneuploidy, a condition in which tumor cells lose or gain chromosomes. Previously, we showed that posttranscriptional silencing by RNAi of pRb1, DNMT12 and MAD2 is associated with aneuploidy in cultured human cells reinforcing the idea that there are several roads leading to aneuploidy. In the attempt to understand if a common molecular signature exists underlying aneuploidy and its tolerance in tumor cells, we induced aneuploidy in human fibroblasts (IMR90) by depleting Rb, MAD2 and DNMT1 genes and analyzed their transcriptome by Microarray (using a p-value of 0.05 and a fold change greater than 2). 1722 differentially expressed genes in the three sample analyzed against control were identified, of which 282 differentially expressed simultaneously in at least two out of three samples analyzed. These 282 genes were analyzed using freeware bioinformatics software (DAVID, GOrilla) that showed the presence of genes involved in many functional group inherent to the inflammatory response, cell proliferation and apoptosis. A detailed analysis of these results (using other system biology tools like Pathway Studio 9, Reactome, STRING) will be shown to get clues about the pathways involved in the generation and tolerance of aneuploidy.