BACKGROUND: Genomic alterations present in pancreatic
adenocarcinoma have been described only partially. In addition, the relations between these alterations and the aggressiveness of the
phenotype remain unknown. METHODS: Genomic
DNA and total
RNA from 5 pancreatic
cell lines, of which 2 have an aggressive
phenotype and are gemcitabine-resistant (Mia-Paca2 and Panc-1), and 3 less aggressive and gemcitabine-sensitive (Capan-1, Capan-2 and BxPC3), have been purified.
DNA abnormalities have been analyzed using an ultra-high-resolution CGH array and
mRNA expression was studied with an Affymetrix GeneChip expression array. RESULTS: We identified 573 amplified and 30 deleted genes common to all 5
cell lines. Some of them have already been described, whereas other genes, implicated in
signal transduction,
apoptosis,
cell cycle or
cell migration, are described for the first time as being related to this cancer. Comparison of genomic abnormalities between the 2 most aggressive and the 3 less aggressive
cell lines led to the identification of 368 genes specifically amplified in the aggressive
cell lines. However, no specific
gene deletion seems to be associated with the aggressive
phenotype. CONCLUSION: Using a high-resolution approach, we could precisely describe the genomic alterations associated with pancreatic
adenocarcinoma and determine those associated with an aggressive
phenotype.