Integrated analysis of expression and genome alteration reveals putative amplified target genes in esophageal cancer

Abstract

Microarray and comparative genomic hybridization (CGH) studies have provided a wide range of information about esophageal cancer, but the correlations between gene expression and copy number alteration are largely unknown. To identify putative amplification target genes in esophageal cancer, a survey of parallel DNA copy number and gene expression in 10 esophageal squamous cell carcinoma (ESCC) cell lines was performed using classical CGH and oligonucleotide microarrays. The gene expression and copy number data were subsequently integrated using signal-to-noise ratio analysis. The results revealed a set of 97 genes with elevated expression levels that were attributable to increased copy number. The set included genes previously reported as overexpressed in cancer as well as several novel genes associated with copy number elevation. These genes are involved in essential cellular processes (e.g., regulation of transcription, signal transduction, cell proliferation, the cell cycle and cell differentiation) that can also have an impact on cancer development. Thus, the integration of DNA and RNA profiles provides a highly productive entry point for the discovery of genes involved in the development and progression of esophageal cancer.