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Context The identification of genes involved in tumorigenesis is essential for the development of new treatment strategies or diagnostic approaches for pancreatic cancer. Objective To identify genes overexpressed in pancreatic cancer we employed differential display, a PCR-based method of differential expression cloning. Using this method, we identified a PCR product that was consistently overexpressed in pancreatic tumors relative to normal pancreatic tissues. Setting Five pancreatic ductal adenocarcinomas and 5 bulk pancreatic ducts isolated from independent pancreatic specimens without malignancies were analyzed by differential display. A panel of 12 pancreatic tumors at various stages of differentiation and a set of 6 pancreatic ducts without malignancies were then used to verify expression by RT-PCR. Results Sequence analysis of a cDNA detected by differential display revealed that it was a portion of the recently cloned gamma-aminobutyric acid A receptor π subunit. RT-PCR analysis of a panel of RNAs prepared from pancreatic ducts isolated from organs without malignancies and pancreatic tumors confirmed that that the gamma-butyric acid A receptor π subunit was significantly overexpressed in pancreatic carcinomas. Analysis of 12 pancreatic tumors revealed that the π subunit was overexpressed in 10 of the tumors (83%). The expression varied among the tumors, however, overexpression was observed in tumors of each histopathological grade. In contrast, none of the normal pancreatic tissues analyzed displayed high levels of expression. Conclusions The expression of the GABAA receptor π subunit may thus play an important role in the pathogenesis of pancreatic cancer.