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Frequent activation of the β‐catenin‐Tcf signaling pathway in nonfamilial colorectal carcinomas with microsatellite instability
Author(s) -
Shitoh Kazuhisa,
Furukawa Taiji,
Kojima Masayuki,
Konishi Fumio,
Miyaki Michiko,
Tsukamoto Toshihiko,
Nagai Hideo
Publication year - 2001
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/1098-2264(2000)9999:9999<::aid-gcc1065>3.0.co;2-i
Subject(s) - microsatellite instability , catenin , mutation , cancer research , wnt signaling pathway , biology , beta catenin , colorectal cancer , microsatellite , gene mutation , gene , genetics , cancer , allele
It has been reported that wild‐type APC protein forms a complex with β‐Catenin and GSK3β, inducing degradation of β‐Catenin in normal cells. Both β‐Catenin and APC gene mutations have recently been shown to activate the same signaling pathway. Frequent mutations of β‐Catenin in hereditary nonpolyposis colorectal carcinomas have also been reported. It was, however, controversial whether the mutation of the β‐Catenin gene was frequent in nonfamilial colorectal carcinomas with high‐frequency microsatellite instability (MSI‐H). We analyzed the mutations of the APC and β‐Catenin genes in 56 nonfamilial colorectal carcinomas stratified according to the presence or absence of microsatellite instability (MSI). APC mutations were identified in 11 of 22 (50%) cases of MSI‐H and 14 of 34 (41%) cases of microsatellite‐stable (MSS)/low‐frequency microsatellite instability (MSI‐L). In contrast, the frequency of β‐Catenin mutations was significantly higher in MSI‐H (6/22; 27%) than in MSS/MSI‐L (1/34; 3%) ( P = 0.01). β‐Catenin mutations were not detected in carcinomas with APC mutation. APC mutation occurred irrespective of MSI status. β‐Catenin mutation, however, occurred frequently in MSI‐H carcinomas. Our data suggest that activation of the β‐Catenin‐Tcf signaling pathway, through either β‐Catenin or APC mutation, frequently contributes to MSI‐H nonfamilial colorectal carcinomas (17/22; 77%). © 2000 Wiley‐Liss, Inc.