Mutation analysis of the cationic trypsinogen gene in patients with pancreatic cancer.
Recently, an Arg to His mutation at residue 117 of the cationic trypsinogen gene (Arg117His) has been shown to be associated with hereditary pancreatitis (hp). A serious complication of hp is development of pancreatic cancer. Patients suffering from hp have been reported to have a 53-fold increased risk to die from pancreatic cancer. However, the quantitative contribution of mutations in the cationic trypsinogen gene to all pancreatic cancer cases is unknown. A relevant contribution of the Arg117His-mutation to pathogenesis of pancreatic cancer might be possible, since also asymptomatic individuals have been reported to carry this mutation and individuals with only mild symptoms may be undiagnosed as hp. In the present study we analyzed genomic DNA obtained from pancreatic cancer tissue from 34 patients and corresponding normal tissue from 28 of these individuals. The third exon of the cationic trypsinogen gene was amplified by nested PCR and digested with 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 positive. Sequencing of the complete third exon of the cationic trypsinogen gene in 10 of the pancreatic cancer patients resulted exclusively in the wild-type sequence. In addition DNA obtained from venous blood of 116 further patients with pancreatic cancer did not carry the Arg117His mutation. Our results 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 (3rd exon) does not contain mutational hot spots.
Hengstler
J G
JG
Institute of Toxicology, University of Mainz, Germany. hengstle@mail-Uni-Mainz.de
Bauer
A
A
Wolf
H K
HK
Bulitta
C J
CJ
Tanner
B
B
Oesch
F
F
Gebhard
S
S
Boettger
T
T
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D001483:Base Sequence; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D015252:Deoxyribonucleases, Type II Site-Specific; D006801:Humans; D008969:Molecular Sequence Data; D010179:Pancreas / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction / Q000379:methods; D014357:Trypsin; D014362:Trypsinogen / Q000235:genetics*
D004273:DNA, Neoplasm; C064831:PRSS2 protein, human; D014362:Trypsinogen; D015252:Deoxyribonucleases, Type II Site-Specific; C092157:endodeoxyribonuclease AflIII; D014357:Trypsin