The pancreatic adenocarcinoma genome harbors multiple amplifications
and deletions, pointing to the existence of numerous oncogenes
and tumor suppressor genes driving the genesis and progression
of this lethal cancer. Here, array comparative genomic hybridization
on a cDNA microarray platform and informatics tools have been
used to define the copy number alterations in a panel of 24 pancreatic
adenocarcinoma cell lines and 13 primary tumor specimens. This
high-resolution genomic analysis has identified all known regional
gains and losses as well as many previously uncharacterized highly
recurrent copy number alterations. A systematic prioritization
scheme has selected 64 focal minimal common regions (MCRs) of
recurrent copy number change. These MCRs possess a median size
of 2.7 megabases (Mb), with 21 (33%) MCRs spanning 1 Mb or less
(median of 0.33 Mb) and possessing an average of 15 annotated
genes. Furthermore, complementary expression profile analysis
of a significant fraction of the genes residing within these 64
prioritized MCRs has enabled the identification of a subset of
candidates with statistically significant association between
gene dosage and mRNA expression. Thus, the integration of DNA
and RNA profiles provides a highly productive entry point for
the discovery of genes involved in the pathogenesis of pancreatic
adenocarcinoma.