K. Shitoh et al., Frequent activation of the beta-catenin-Tcf signaling pathway in nonfamilial colorectal carcinomas with microsatellite instability, GENE CHROM, 30(1), 2001, pp. 32-37
It has been reported that wild-type APC protein forms a complex with beta -
Catenin and GSK3 beta, inducing degradation of beta -Catenin in normal cell
s. Both beta -Catenin and APC gene mutations have recently been shown to ac
tivate the same signaling pathway. Frequent mutations of beta -Catenin in h
ereditary nonpolyposis colorectal carcinomas have also been reported. It wa
s, however, controversial whether the mutation of the beta -Catenin gene wa
s frequent in nonfamilial colorectal carcinomas with high-frequency microsa
tellite instability (MSI-H). We analyzed the mutations of the APC and beta
-Catenin genes in 56 nonfamilial colorectal carcinomas stratified according
to the presence or absence of microsatellite instability (MSI). APC mutati
ons were identified in 11 of 22 (50%) cases of MSI-H and 14 of 34 (41%) cas
es of microsatellite-stable (MSS)/low-frequency microsatellite instability
(MSI-L). In contrast, the frequency of beta -Catenin mutations was signific
antly higher in MSI-H (6/22; 27%) than in MSS/MSI-L (1/34; 3%) (P = 0.01).
beta -Catenin mutations were not detected in carcinomas with APC mutation.
APC mutation occurred irrespective of MSI status. beta -Catenin mutation, h
owever, occurred frequently in MSI-H carcinomas. Our data suggest that acti
vation of the beta -Catenin-Tcf signaling pathway, through either beta -Cat
enin or APC mutation, frequently contributes to MSI-H nonfamilial colorecta
l carcinomas (17/22; 72%). (C) 2001 Wiley-Liss, Inc.