A Method for Finding Putative Causes of Gene Expression Variation

The majority of microarray studies evaluate gene expression differences between various specimens or conditions. However, the causes of this variability often remain unknown. Our aim is to identify underlying causes of these patterns, a process that would eventually enable a mechanistic understanding of the deregulation of gene expression in cancer. The procedure consists of three phases: pre-processing, data integration and statistical analysis. We have applied the strategy to identify genes that are overexpressed due to amplification in breast cancer. The data were obtained from 14 breast cancer cell lines, which were subjected to cDNA microarray based copy number and expression experiments. The result of the analysis was a list that consisted of 92 genes. This set includes several genes that are known to be both overexpressed and amplified in breast cancer. The complete study was published in Journal of the Franklin Institute 2004 [1], and in this paper we focus on the main issues of the study.