title: Frequent mutation of beta-catenin and APC genes in primary colorectal tumors from patients with hereditary nonpolyposis colorectal cancer.
abstract: Hereditary nonpolyposis colorectal cancer (HNPCC) is characterized by defective DNA mismatch repair, which results in genetic instability of tumors; however, only a few target genes have been recognized. Our previous study detected a low frequency of APC gene mutation (21%) in colorectal tumors from HNPCC patients, in contrast to a high frequency of APC gene alteration (>70%) in non-HNPCC tumors. Because both beta-catenin and ACP gene mutations have recently been shown to activate the same signaling pathway, we analyzed beta-catenin mutation in HNPCC tumors. A notable frequency of beta-catenin gene mutation (43%, 12 of 28) was found to occur in HNPCC colorectal tumors. Beta-catenin mutations were not detected in tumors with APC mutations. All beta-catenin mutations detected in HNPCC tumors existed within the regulatory domain of beta-catenin. Immunohistochemical staining of tumors with this mutation showed accumulation of beta-catenin protein in nuclei. These and previous data from our laboratory suggest that activation of the beta-catenin-Tcf signaling pathway, through either beta-catenin or APC mutation, contributes to HNPCC colorectal carcinogenesis in approximately 65% of cases.
authors.affiliation: Hereditary Tumor Research Project, Tokyo Metropolitan Komagome Hospital, Japan. mmiyaki@opal.famille.ne.jp
authors.forename: M
authors.initials: M
authors.lastname: Miyaki
authors.forename: T
authors.initials: T
authors.lastname: Iijima
authors.forename: J
authors.initials: J
authors.lastname: Kimura
authors.forename: M
authors.initials: M
authors.lastname: Yasuno
authors.forename: T
authors.initials: T
authors.lastname: Mori
authors.forename: Y
authors.initials: Y
authors.lastname: Hayashi
authors.forename: M
authors.initials: M
authors.lastname: Koike
authors.forename: N
authors.initials: N
authors.lastname: Shitara
authors.forename: T
authors.initials: T
authors.lastname: Iwama
authors.forename: T
authors.initials: T
authors.lastname: Kuroki
mesh_terms: D020137:Base Pair Mismatch; D015820:Cadherins / Q000235:genetics; D003111:Colonic Polyps / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics* / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004268:DNA-Binding Proteins; D017491:Genes, APC; D018095:Germ-Line Mutation; D006801:Humans; D007564:Japan; D051718:MutS Homolog 2 Protein; D009154:Mutation; D009361:Neoplasm Invasiveness; D011518:Proto-Oncogene Proteins / Q000235:genetics; D015534:Trans-Activators; D051176:beta Catenin
chemical_list: C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D051176:beta Catenin; C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein