Frequent mutation of β-catenin and APC genes in primary colorectal tumors from patients with hereditary nonpolyposis colorectal cancer

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...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1999-09, Vol.59 (18), p.4506-4509
Main Authors: MIYAKI, M, IIJIMA, T, KIMURA, J, YASUNO, M, MORI, T, HAYASHI, Y, KOIKE, M, SHITARA, N, IWAMA, T, KUROKI, T
Format: Article
Language:English
Subjects:
APC gene
b-catenin
Base Pair Mismatch
beta Catenin
Biological and medical sciences
Cadherins - genetics
Colonic Polyps - genetics
Colorectal Neoplasms - genetics
Colorectal Neoplasms - pathology
Colorectal Neoplasms, Hereditary Nonpolyposis - genetics
Colorectal Neoplasms, Hereditary Nonpolyposis - pathology
Cytoskeletal Proteins - genetics
DNA-Binding Proteins
Gastroenterology. Liver. Pancreas. Abdomen
Genes, APC
Germ-Line Mutation
Humans
Japan
Medical sciences
Mutation
MutS Homolog 2 Protein
Neoplasm Invasiveness
Proto-Oncogene Proteins - genetics
Stomach. Duodenum. Small intestine. Colon. Rectum. Anus
Trans-Activators
Tumors
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Summary: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.
ISSN:0008-5472
1538-7445