Identification of genomic alterations associated with the aggressiveness of pancreatic cancer using an ultra-high-resolution CGH array.

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.