Analysis of K-ras gene mutation in hyperplastic duct cells of the pancreas without pancreatic disease.
OBJECTIVE
We and others have previously shown that the mutation of K-ras codon 12 was found in the majority of pancreatic adenocarcinomas. The mutation has also been identified in the pancreatic duct with mucous cell hyperplasia in association with chronic pancreatitis. Ductal hyperplasia is also frequently found in the pancreas free from pancreatic carcinoma or chronic pancreatitis. The aim of this study was to assess the incidence and types of mutations in hyperplastic foci in these cases.


METHODS
The nucleotide sequence of the K-ras gene at codon 12 of the DNA extracted from microdissected hyperplastic epithelium of the pancreatic duct obtained at autopsy in patients without pancreatic adenocarcinoma or chronic pancreatitis was analyzed.


RESULTS
Of 38 patients with 79 hyperplastic foci, 12 patients (with 19 hyperplastic foci) had mutations. None of the 16 normal ducts in 12 specimens had this mutation. The nucleotide sequence of the codon in 53% of ductal hyperplastic foci was TGT or AGT, both of which were not found in 30 cases of adenocarcinoma.


CONCLUSIONS
These results suggest that the ras gene mutation occurs frequently in multifocal hyperplastic foci of pancreatic duct and that the mutations may not have direct relevance to the carcinogenesis of pancreatic cancer.
Second Department of Medicine, Faculty of Medicine, University of Tokyo, Japan.
M
M
Tada
M
M
Ohashi
Y
Y
Shiratori
T
T
Okudaira
Y
Y
Komatsu
T
T
Kawabe
H
H
Yoshida
R
R
Machinami
K
K
Kishi
M
M
Omata
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D005260:Female; D005787:Gene Frequency; D011905:Genes, ras; D006801:Humans; D006965:Hyperplasia; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010183:Pancreatic Ducts / Q000473:pathology* / Q000503:physiopathology*