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Department of Hygiene and Oncology, Tokyo Medical and Dental University School of Medicine, Yushima, Bunkyo-ku, Tokyo 113 [Y. A., H. N., Y. Y.]; 2nd Department of Surgery, Fukushima Medical College, Hikarigaoka, Fukushima, Fukushima 960-12 [H. S., A. T., R. A.]; and Department of Surgery, Ota Memorial Hospital, Nakamachi, Koriyama, Fukushima 963 [T. Y.], Japan
A germ-line mutation of hMSH6 (also called GTBP) was found in a hereditary nonpolyposis colorectal cancer (HNPCC)-like patient in whom germ-line mutations of hMSH2, hMSH3, or hMLH1 had not been detected. The patient had rectal cancer and two colon adenomas at 62 years of age and a weak family history of gastrointestinal tumors, indicating atypical HNPCC. Somatic mutations of hMSH6 were observed in three colorectal tumors from the patient, indicating two-hit inactivation. Microsatellite instabilities at mononucleotide repeats were detected in all three tumors. These data suggest that hMSH6 is responsible for tumorigenesis in atypical HNPCC.
1 Supported in part by a Grant-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Science, Sports and Culture of Japan (to Y. A. and Y. Y.) and by a research grant from the Princess Takamatsu Cancer Research Fund (to Y. Y.).
2 To whom requests for reprints should be addressed, at Department of Hygiene and Oncology, Tokyo Medical and Dental University School of Medicine, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113, Japan. Phone: 81-3-5803-5182; Fax: 81-3-5803-0125; E-mail: yyuasa.hgen@med.tmd.ac.jp.
Received 6/13/97. Accepted 7/31/97.
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J. Genschel, S. J. Littman, J. T. Drummond, and P. Modrich Isolation of MutSbeta from Human Cells and Comparison of the Mismatch Repair Specificities of MutSbeta and MutSalpha J. Biol. Chem., July 31, 1998; 273(31): 19895 - 19901. [Abstract] [Full Text] [PDF]
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L. A. Aaltonen, R. Salovaara, P. Kristo, F. Canzian, A. Hemminki, P. Peltomaki, R. B. Chadwick, H. Kaariainen, M. Eskelinen, H. Jarvinen, et al. Incidence of Hereditary Nonpolyposis Colorectal Cancer and the Feasibility of Molecular Screening for the Disease N. Engl. J. Med., May 21, 1998; 338(21): 1481 - 1487. [Abstract] [Full Text] [PDF]
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