Somatic mutations of the trefoil factor family 1 gene in gastric cancer.
OBJECTIVE
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.
Park
W S
WS
Department of Pathology and Genetic Oncology Laboratory, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Oh
R R
RR
Park
J Y
JY
Lee
J H
JH
Shin
M S
MS
Kim
H S
HS
Lee
H K
HK
Kim
Y S
YS
Kim
S Y
SY
Lee
S H
SH
Yoo
N J
NJ
Lee
J Y
JY
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence / Q000235:genetics; D001483:Base Sequence / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology; D006133:Growth Substances / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009077:Mucins; D005810:Multigene Family; D009124:Muscle Proteins; D009154:Mutation / Q000235:genetics*; D009479:Neuropeptides; D010455:Peptides / Q000235:genetics* / Q000378:metabolism; D012016:Reference Values; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3
D006133:Growth Substances; D009077:Mucins; D009124:Muscle Proteins; D009479:Neuropeptides; D010455:Peptides; C099037:TFF3 protein, rat; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3