Frequent somatic mutations of the beta-catenin gene in intestinal-type gastric cancer.
The increased level of cytoplasmic beta-catenin through the mutations to either beta-catenin or adenomatous polyposis coli (APC) has been proposed as an important oncogenic step in various tumors. Gastric cancer showed frequent genetic alterations of the APC gene, and the risk for gastric cancer in familial adenomatosus polyposis patients is 10 times higher than that in the general population. These findings raise the possibility that mutations of beta-catenin may also be associated with the development of gastric cancer. We detected seven somatic mutations in a portion of exon 3 encoding for the glycogen synthase kinase 3beta phosphorylation consensus region of the beta-catenin gene in 43 gastric cancers. All of these mutations were missense mutations, of which five are in the highly conserved aspartic acid 32 and two are in serine 29; all of these seven mutations were detected exclusively in intestinal-type gastric cancers (7 of 26; 26.9%), but not in the diffuse-type (0 of 17). We concluded that disruption of the APC/beta-catenin/T cell factor-lymphoid enhancer binding factor pathway might play an important role especially in the development of intestinal-type gastric cancer.
Park
W S
WS
Department of Pathology and Cancer Research Institute, Catholic University Medical College, Seoul, Korea.
Oh
R R
RR
Park
J Y
JY
Lee
S H
SH
Shin
M S
MS
Kim
Y S
YS
Kim
S Y
SY
Lee
H K
HK
Kim
P J
PJ
Oh
S T
ST
Yoo
N J
NJ
Lee
J Y
JY
D001483:Base Sequence; D003598:Cytoskeletal Proteins / Q000235:genetics*; D017491:Genes, APC; D006801:Humans; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D013274:Stomach Neoplasms / Q000235:genetics*; D015534:Trans-Activators; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin