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

Genes Chromosomes Cancer. 2001 Jan;30(1):32-7. doi: 10.1002/1098-2264(2000)9999:9999<::aid-gcc1065>;2-i.


It has been reported that wild-type APC protein forms a complex with beta-Catenin and GSK3beta, inducing degradation of beta-Catenin in normal cells. Both beta-Catenin and APC gene mutations have recently been shown to activate the same signaling pathway. Frequent mutations of beta-Catenin in hereditary nonpolyposis colorectal carcinomas have also been reported. It was, however, controversial whether the mutation of the beta-Catenin gene was frequent in nonfamilial colorectal carcinomas with high-frequency microsatellite 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 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 beta-Catenin mutations was significantly 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, however, occurred frequently in MSI-H carcinomas. Our data suggest that activation of the beta-Catenin-Tcf signaling pathway, through either beta-Catenin or APC mutation, frequently contributes to MSI-H nonfamilial colorectal carcinomas (17/22; 77%).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cadherins / genetics
  • Colorectal Neoplasms / genetics*
  • Cytoskeletal Proteins / genetics*
  • DNA-Binding Proteins / genetics
  • Gene Expression Regulation, Neoplastic*
  • Genes, APC / genetics
  • Humans
  • Lymphoid Enhancer-Binding Factor 1
  • Microsatellite Repeats / genetics*
  • Mutation / genetics
  • Polymerase Chain Reaction
  • Polymorphism, Single-Stranded Conformational
  • Signal Transduction / genetics*
  • Trans-Activators*
  • Transcription Factors / genetics
  • beta Catenin


  • CTNNB1 protein, human
  • Cadherins
  • Cytoskeletal Proteins
  • DNA-Binding Proteins
  • Lymphoid Enhancer-Binding Factor 1
  • Trans-Activators
  • Transcription Factors
  • beta Catenin