PMID- 10493496
OWN - NLM
STAT- MEDLINE
DCOM- 19991008
LR  - 20061115
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 59
IP  - 18
DP  - 1999 Sep 15
TI  - Frequent mutation of beta-catenin and APC genes in primary colorectal tumors from 
      patients with hereditary nonpolyposis colorectal cancer.
PG  - 4506-9
AB  - 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.
FAU - Miyaki, M
AU  - Miyaki M
AD  - Hereditary Tumor Research Project, Tokyo Metropolitan Komagome Hospital, Japan. 
      mmiyaki@opal.famille.ne.jp
FAU - Iijima, T
AU  - Iijima T
FAU - Kimura, J
AU  - Kimura J
FAU - Yasuno, M
AU  - Yasuno M
FAU - Mori, T
AU  - Mori T
FAU - Hayashi, Y
AU  - Hayashi Y
FAU - Koike, M
AU  - Koike M
FAU - Shitara, N
AU  - Shitara N
FAU - Iwama, T
AU  - Iwama T
FAU - Kuroki, T
AU  - Kuroki T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (CTNNB1 protein, human)
RN  - 0 (Cadherins)
RN  - 0 (Cytoskeletal Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Trans-Activators)
RN  - 0 (beta Catenin)
RN  - EC 3.6.1.3 (MSH2 protein, human)
RN  - EC 3.6.1.3 (MutS Homolog 2 Protein)
SB  - IM
MH  - Base Pair Mismatch
MH  - Cadherins/genetics
MH  - Colonic Polyps/genetics
MH  - Colorectal Neoplasms/*genetics/pathology
MH  - Colorectal Neoplasms, Hereditary Nonpolyposis/*genetics/pathology
MH  - Cytoskeletal Proteins/*genetics
MH  - *DNA-Binding Proteins
MH  - *Genes, APC
MH  - Germ-Line Mutation
MH  - Humans
MH  - Japan
MH  - MutS Homolog 2 Protein
MH  - *Mutation
MH  - Neoplasm Invasiveness
MH  - Proto-Oncogene Proteins/genetics
MH  - *Trans-Activators
MH  - beta Catenin
EDAT- 1999/09/24 00:00
MHDA- 1999/09/24 00:01
CRDT- 1999/09/24 00:00
PHST- 1999/09/24 00:00 [pubmed]
PHST- 1999/09/24 00:01 [medline]
PHST- 1999/09/24 00:00 [entrez]
PST - ppublish
SO  - Cancer Res. 1999 Sep 15;59(18):4506-9.