High-resolution genomic and expression profiling reveals 105 putative amplification target genes in pancreatic cancer - PubMed (original) (raw)

High-resolution genomic and expression profiling reveals 105 putative amplification target genes in pancreatic cancer

Eija H Mahlamäki et al. Neoplasia. 2004 Sep-Oct.

Abstract

Comparative genomic hybridization (CGH) studies have provided a wealth of information on common copy number aberrations in pancreatic cancer, but the genes affected by these aberrations are largely unknown. To identify putative amplification target genes in pancreatic cancer, we performed a parallel copy number and expression survey in 13 pancreatic cancer cell lines using a 12,232-clone cDNA microarray, providing an average resolution of 300 kb throughout the human genome. CGH on cDNA microarray allowed highly accurate mapping of copy number increases and resulted in identification of 24 independent amplicons, ranging in size from 130 kb to 11 Mb. Statistical evaluation of gene copy number and expression data across all 13 cell lines revealed a set of 105 genes whose elevated expression levels were directly attributable to increased copy number. These included genes previously reported to be amplified in cancer as well as several novel targets for copy number alterations, such as p21-activated kinase 4 (PAK4), which was previously shown to be involved in cell migration, cell adhesion, and anchorage-independent growth. In conclusion, our results implicate a set of 105 genes that is likely to be actively involved in the development and progression of pancreatic cancer.

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Figures

Figure 1

Figure 1

Gene copy number and expression analysis for chromosome 19 in the Panc1 pancreatic cancer cell line by cDNA microarray. The copy number ratios were plotted as a function of the position of the cDNA clones along chromosome 19. In (A), individual data points were connected with a line. The inset shows chromosomal CGH copy number ratio profile. In (B), individual data points were color-coded according to cDNA expression ratios. The red dots indicate overexpressed genes (the upper 7% of expression ratios) and the green dots indicate underexpressed genes (lowest 7% of expression ratios) in Panc1 cells.

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