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.


CONCLUSIONS
Using a high-resolution approach, we could precisely describe the genomic alterations associated with pancreatic adenocarcinoma and determine those associated with an aggressive phenotype.
Legoffic
Aude
A
INSERM U.624, Stress Cellulaire, Parc Scientifique et Technologique de Luminy, Marseille, France.
Calvo
Ezequiel Luis
EL
Barthet
Marc
M
Delpero
Jean-Robert
JR
Dagorn
Jean Charles
JC
Iovanna
Juan Lucio
JL
D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D002874:Chromosome Mapping; D002877:Chromosomes, Human / Q000235:genetics; D041321:Chromosomes, Human, X; D055028:Comparative Genomic Hybridization / Q000379:methods*; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D004351:Drug Resistance; D014644:Genetic Variation; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D012680:Sensitivity and Specificity; D015996:Survival Rate; D000093542:Gemcitabine
D012333:RNA, Messenger; D012334:RNA, Neoplasm; D003841:Deoxycytidine; D000093542:Gemcitabine