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[Cancer Research 59, 4506-4509, September 1, 1999]
© 1999 American Association for Cancer Research
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[Cancer Research 59, 4506-4509, September 15, 1999]
© 1999 American Association for Cancer Research

Advances in Brief

Frequent Mutation of ß-Catenin and APC Genes in Primary Colorectal Tumors from Patients with Hereditary Nonpolyposis Colorectal Cancer1

Michiko Miyaki2, Takeru Iijima, Junko Kimura, Masamichi Yasuno, Takeo Mori, Yukiko Hayashi, Morio Koike, Nobuyuki Shitara, Takeo Iwama and Toshio Kuroki

Hereditary Tumor Research Project [M. M., T. Ii., J. K.] and Departments of Surgery [M. Y., T. M.], Pathology [Y. H., M. K.], and Neurosurgery [N. S.], Tokyo Metropolitan Komagome Hospital, Tokyo 113-8677; Kyoundo Hospital Sasaki Institute, Tokyo 101-0062 [T. Iw.]; and Institute of Molecular Oncology, Showa University, Tokyo 142-8555 [M. M., T. Ii., T. K.], Japan.

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 ß-catenin and ACP gene mutations have recently been shown to activate the same signaling pathway, we analyzed ß-catenin mutation in HNPCC tumors. A notable frequency of ß-catenin gene mutation (43%, 12 of 28) was found to occur in HNPCC colorectal tumors. ß-Catenin mutations were not detected in tumors with APC mutations. All ß-catenin mutations detected in HNPCC tumors existed within the regulatory domain of ß-catenin. Immunohistochemical staining of tumors with this mutation showed accumulation of ß-catenin protein in nuclei. These and previous data from our laboratory suggest that activation of the ß-catenin-Tcf signaling pathway, through either ß-catenin or APC mutation, contributes to HNPCC colorectal carcinogenesis in ~65% of cases.




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HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
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Annual Meeting Education Book Meeting Abstracts Online
Copyright © 1999 by the American Association for Cancer Research.