Background & Aims: There is increasing evidence that trefoil factor family
1 (TFF1) is a stabilizer of the mucous gel overlying the gastrointestinal m
ucosa that provides a physical barrier against various noxious agents. TFF1
knockout mice developed multiple gastric adenomas and carcinomas, suggesti
ng that TFF1 is a gastric-specific tumor-suppressor gene. Methods: We analy
zed the somatic mutations and loss of heterozygosity (LOH) of the TFF1 gene
using an intragenic polymorphic marker in 61 gastric tumors. The expressio
n pattern of TFF1 was also examined by immunohistochemistry. Results: We de
tected a total of 8 somatic mutations-1 (5.5%) of 18 adenomas and 7 (16.3%)
of 43 carcinomas-that were all missense mutations confined to the loop I a
nd loop II structure of TFF1. We detected LOH in 5 (1 in adenoma and 4 in c
ancer) of 30 (16.7%) informative gastric tumors with an intragenic polymorp
hic marker -2 base pairs (bp) upstream of the coding region of the TFF1 gen
e. Although 2 cases were noninformative, the 7 gastric cancers with mutatio
n seemed to show the loss of the remaining allele except in 1 case, suggest
ing that TFF1 is a tumor-suppressor gene, We found loss of TFF1 expression
in 44.2% of the gastric carcinomas, but there is no correlation between imm
unoreactivity and genetic alterations of the TFF1 gene. Conclusions: These
results indicate that genetic alterations of TFF1 may lead to gastric mucos
al barrier defects and contribute to the pathogenesis of gastric cancer.