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Predominant germ‐line mutation of the hMSH2 gene in Japanese hereditary non‐polyposis colorectal cancer kindreds
Author(s) -
Bai YunQing,
Akiyama Yoshimitsu,
Nagasaki Hiromi,
Lu ShiLong,
Arai Takehiro,
Morisaki Takashi,
Kitamura Masatoshi,
Muto Atsushi,
Nagashima Michio,
Nomizu Tadashi,
Iwama Takeo,
Itoh Hideaki,
Baba Shozo,
Iwai Takehisa,
Yuasa Yasuhito
Publication year - 1999
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19990812)82:4<512::aid-ijc7>3.0.co;2-8
Subject(s) - genetics , mutation , colorectal cancer , germline , germline mutation , cancer , gene , biology , cancer research , medicine
By means of PCR‐SSCP and direct sequencing, we detected 12 germ‐line mutations of hMSH2 or hMLH1 in 37 Japanese hereditary non‐polyposis colorectal cancer (HNPCC) kindreds, of whom 15 satisfied the Amsterdam and 22 the Japanese criteria. The germ‐line mutation detection rate of hMSH2 was much higher than that of hMLH1 (11/37 vs . 1/37). The total mutation detection rate of hMSH2 and hMLH1 in the Amsterdam criteria group was significantly higher than that in the Japanese criteria group (9/15 vs . 3/22). Furthermore, the mean age of the HNPCC patients in the mutation‐positive group was lower than that in the mutation‐negative one; the rates of both vertical transmission and multiplicity of tumors in the mutation‐positive group were higher than those in the mutation‐negative one. In addition, the number of patients with microsatellite instability–positive cancers in the mutation‐positive group was higher than that in the mutation‐negative one. Our results suggest firstly that the hMSH2 gene plays a much more important role than hMLH1 in the carcinogenesis of Japanese HNPCC patients, secondly that the rate of hMSH2 and hMLH1 mutations is high in the kindreds satisfying the Amsterdam criteria and thirdly that both the clinical phenotypes (early onset, vertical transmission and multiplicity of tumors) and the microsatellite instability status are important for the genetic screening of HNPCC. Int. J. Cancer 82:512–515, 1999. © 1999 Wiley‐Liss, Inc.