ABSTRACT: To identify genomic abnormalities characteristic of pancreatic ductal adenocarcinoma (PDAC) in vivo, a panel of 27 microdissected PDAC specimens were analyzed using high-density microarrays representing ~116 000 single nucleotide polymorphism (SNP) loci. We detected frequent gains of 1q, 2, 3, 5, 7p, 8q, 11, 14q and 17q (>78% of cases), and losses of 1p, 3p, 6, 9p, 13q, 14q, 17p and 18q (>44%). Although the results were comparable with those from array CGH, regions of those genetic changes were defined more accurately by SNP arrays. Integrating the Ensembl public data, we have generated "gene" copy number indices that facilitate the search for novel candidates involved in pancreatic carcinogenesis. Copy numbers in a subset of the genes were validated using quantitative real-time PCR. The SKAP2/SCAP2 gene (7p15.2), which belongs to the src family kinases, was most frequently (63%) amplified in our sample set and its recurrent over-expression (67%) was confirmed by reverse transcription-PCR. Furthermore, fluorescence in situ hybridization and in situ RNA hybridization analyses for this gene have demonstrated a significant correlation between DNA copy number and mRNA expression level in an independent sample set (p<0.001). These findings indicate that the dysregulation of SKAP2/SCAP2, which is mostly caused by its increased gene copy number, is likely to be associated with the development of PDAC. Experiment Overall Design: A total of 27 fresh-frozen PDAC tissue specimens were obtained surgically or at autopsy from Yamaguchi University School of Medicine, Japan. All the tissues were confirmed histologically by a pathologist. Tissue microdissection was manually performed to collect more than 90% of tumor cells in all cases and DNA was extracted using a DNA extraction kit (SepaGene). Reference DNA was obtained from lymphocytes of total 13 healthy volunteers (six males and seven females). To assess DNA copy number alterations and LOH, we used the Copy Number Analyzer for Affymetrix GeneChip® (CNAG, Ver2.0) software (Nannya et al. Cancer Res. 2005 Jul 15;65(14):6071-9). Experiment Overall Design: The following Samples were added to the Series after this study was published: PC5_Hind (GSM278031), PC5_Xba (GSM278032), PC11-Hind (GSM278043), and PC19_Hind (GSM278057). A supplementary file describing the clinical data of 28 microdissected PDAC samples is linked at the bottom of the Series.