Study of chromosomal aberrations and gene expression changes in gastric cancer cell lines using cDNA microarray

Abstract

Parallel analysis of gene expression and chromosomal copy number changes at high resolution in a genomic scale is possible using cDNA microarray, and may improve our understanding about the relationship between chromosomal alteration and gene expression. We have previously profiled the gene expression of gastric cancer (GC) cell lines and 90 GC tumor samples in comparison to non-tumor gastric mucosa. In this study, we profiled the chromosomal copy number changes in 10 GC cell lines using the same cDNA microarray. Parallel analysis has led to the identification of genes that were both amplified (defined by gain of at least 4 copies of chromosome) and over-expressed (at least 2 fold induction across the mean expression of a group of GC, gastric mucosa and GC cell lines) in each of the GC cell line. The expression levels of these genes in a large panel of GC compared to non-tumour gastric mucosae were also examined. Genes that were both amplified and up-regulated in GC cell lines revealed those residing in several chromosomal regions previously known to be amplified in GC, and a few other un-reported sites. Apart from genes that were presumptive target of amplification in each of these known amplicons, such as MET in 7q31, MYC in 8q24, FGFR2 in 10q26, CD44 in 11p13 and ERBB2 in 17q11, which all showed consistent amplification and up-regulation, there were wide range of variation in size and complexity of each amplicon in terms of the number of genes involved and up-regulated. For example, the amplicon in 10q26 was very small and contained only several up-regulated genes. The amplicon in 7q, 11p and 17q spanned a larger chromosomal region with many up-regulated genes. Furthermore, many of the genes residing in these amplicons showed significant up-regulation in GC compared with non-tumor gastric mucosa. Our data suggest that the net effect of chromosomal amplification may not necessarily be limited to up-regulation of a single gene, and the combined effect of the gene expression changes may contribute to the carcinogenic process. Thus, combining gene expression profiling and cDNA-array based comparative genomic hybridization can offer a comprehensive strategy for understanding the complex process of chromosomal aberrations and their effects in tumorigenesis.