Frequent activation of the beta-catenin-Tcf signaling pathway in nonfamilial colorectal carcinomas with microsatellite instability

Shitoh, K Furukawa, T Kojima, M Konishi, F Miyaki, M Tsukamoto, T Nagai, H

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

25

INGLESE

Article

Onconogenesis & Cancer Research

GENES CHROMOSOMES & CANCER

1045-2257 → ACNP

30

1

2001

32 - 37

ISI

1045-2257(200101)30:1<32:FAOTBS>2.0.ZU;2-T

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.