BACKGROUND & AIMS: There is increasing evidence that trefoil factor family 1 (TFF1) is a stabilizer of the mucous gel overlying the gastrointestinal mucosa that provides a physical barrier against various noxious agents. TFF1 knockout mice developed multiple gastric adenomas and carcinomas, suggesting that TFF1 is a gastric-specific tumor-suppressor gene. METHODS: We analyzed the somatic mutations and loss of heterozygosity (LOH) of the TFF1 gene using an intragenic polymorphic marker in 61 gastric tumors. The expression pattern of TFF1 was also examined by immunohistochemistry. RESULTS: We detected 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 and loop II structure of TFF1. We detected LOH in 5 (1 in adenoma and 4 in cancer) of 30 (16.7%) informative gastric tumors with an intragenic polymorphic marker -2 base pairs (bp) upstream of the coding region of the TFF1 gene. Although 2 cases were noninformative, the 7 gastric cancers with mutation seemed to show the loss of the remaining allele except in 1 case, suggesting 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 immunoreactivity and genetic alterations of the TFF1 gene. CONCLUSIONS: These results indicate that genetic alterations of TFF1 may lead to gastric mucosal barrier defects and contribute to the pathogenesis of gastric cancer.
BACKGROUND & AIMS: There is increasing evidence that trefoil factor family 1 (TFF1) is a stabilizer of the mucous gel overlying the gastrointestinal mucosa that provides a physical barrier against various noxious agents. TFF1 knockout mice developed multiple gastric adenomas and carcinomas, suggesting that TFF1 is a gastric-specific tumor-suppressor gene. METHODS: We analyzed the somatic mutations and loss of heterozygosity (LOH) of the TFF1 gene using an intragenic polymorphic marker in 61 gastric tumors. The expression pattern of TFF1 was also examined by immunohistochemistry. RESULTS: We detected 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 and loop II structure of TFF1. We detected LOH in 5 (1 in adenoma and 4 in cancer) of 30 (16.7%) informative gastric tumors with an intragenic polymorphic marker -2 base pairs (bp) upstream of the coding region of the TFF1 gene. Although 2 cases were noninformative, the 7 gastric cancers with mutation seemed to show the loss of the remaining allele except in 1 case, suggesting 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 immunoreactivity and genetic alterations of the TFF1 gene. CONCLUSIONS: These results indicate that genetic alterations of TFF1 may lead to gastric mucosal barrier defects and contribute to the pathogenesis of gastric cancer.
Authors: Mohammed Soutto; Abbes Belkhiri; M Blanca Piazuelo; Barbara G Schneider; Dunfa Peng; Aixiang Jiang; M Kay Washington; Yasin Kokoye; Sheila E Crowe; Alexander Zaika; Pelayo Correa; Richard M Peek; Wael El-Rifai Journal: J Clin Invest Date: 2011-04-01 Impact factor: 14.808
Authors: Charles A Fox; Lisa M Sapinoso; Hong Zhang; Wanghai Zhang; Howard L McLeod; Gina R Petroni; Tarun Mullick; Christopher A Moskaluk; Henry F Frierson; Garret M Hampton; Steven M Powell Journal: Neoplasia Date: 2005-04 Impact factor: 5.715
Authors: James J Farrell; Douglas Taupin; Theodore J Koh; Duan Chen; Chun-Mei Zhao; Daniel K Podolsky; Timothy C Wang Journal: J Clin Invest Date: 2002-01 Impact factor: 14.808
Authors: Olga Kim; Jung Hwan Yoon; Won Suk Choi; Hassan Ashktorab; Duane T Smoot; Suk Woo Nam; Jung Young Lee; Won Sang Park Journal: Gastric Cancer Date: 2017-02-01 Impact factor: 7.370
Authors: James G Fox; Arlin B Rogers; Mark T Whary; Zhongming Ge; Masa Ohtani; Evelyn Kurt Jones; Timothy C Wang Journal: Am J Pathol Date: 2007-11 Impact factor: 4.307