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[Cancer Research 57, 3920-3923, September 15, 1997]
© 1997 American Association for Cancer Research
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Germ-Line Mutation of the hMSH6/GTBP Gene in an Atypical Hereditary Nonpolyposis Colorectal Cancer Kindred1

Yoshimitsu Akiyama, Hisayoshi Sato, Toshio Yamada, Hiromi Nagasaki, Atsuo Tsuchiya, Rikiya Abe and Yasuhito Yuasa2

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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