Somatic mutations of the trefoil factor family 1 gene in gastric cancer

Citation
Ws. Park et al., Somatic mutations of the trefoil factor family 1 gene in gastric cancer, GASTROENTY, 119(3), 2000, pp. 691-698
Citations number
29
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Gastroenerology and Hepatology","da verificare
Journal title
GASTROENTEROLOGY
ISSN journal
0016-5085 → ACNP
Volume
119
Issue
3
Year of publication
2000
Pages
691 - 698
Database
ISI
SICI code
0016-5085(200009)119:3<691:SMOTTF>2.0.ZU;2-J
Abstract
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.