Mutation analysis of the cationic trypsinogen gene in patients with pancreatic cancer

Recently, an Alg to His mutation at residue 117 of the cationic trypsinogen gene (Arg117His) has been shown to be associated with hereditary pancreati tis (hp). A serious complication of hp is development of pancreatic cancer: Patients suffering from om hp have been reported to have a 53-fold increas ed risk to die fi om pancreatic cancel: However, the quantitative contribut ion of mutations in the cationic trypsinogen gene to all pancreatic cancel cases is unknown. A relevant contribution of the Arg117His-mutation to path ogenesis of pancreatic cancer might be possible, since also asymptomatic in dividuals have been reported to carry this mutation and individuals with on ly mild symptoms may be undiagnosed as: hp. In the present study we analyze d genomic DNA obtained fi om pancreatic cancer tissue fi om 34 patients and corresponding normal tissue fi om 28 of these individuals. The third exon of the cationic trypsinogen gene was amplified by nested PCR and digested w ith AflIII, since the Arg117His mutation creates an AflIII-restriction site . None of the examined samples carried the Arg117His mutation, whereas the amplification product obtained from a patient with known hp was clearly pos itive. Sequencing of the complete third exon of the cationic trypsinogen ge ne in 10 of the pancreatic cancer patients resulted exclusively in the wild -type sequence. In addition DNA obtained from venous blood of 116 further p atients with pancreatic cancel did not carry the Arg117His mutation. Our re sults show that the Arg117His mutation does not contribute to pathogenesis of a substantial fraction of all pancreatic adenocarcinomas. In contrast to most oncogenes or tumor suppressor genes the cationic trypsinogen gene (3r d exon) does not contain mutational hot spots.