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Frequent Replication Errors at Microsatellite Loci in Tumors of Patients with Multiple Primary Cancers¹

Departments of Biochemistry [A. H., H-J. H., M. S., Y. N.], Pathology [A. Y., Y. K.], and Surgery [H. O.], Cancer Institute, I-37-1 Kami-Ikebukuro, Toshima-ku, Tokyo 170, and First Department of Pathology, Hiroshima University School of Medicine, 1-2-3, Kasumi, Minami-ku, Hiroshima 734 [W. Y., E. T.], Japan

Nearly 10% of cancer patients develop a second primary cancer within 10 years after surgical removal of the first tumor. Hence, detection of a genetic risk for developing multiple primary tumors would be of clinical importance. To investigate whether a genetic defect(s) involving the mismatch repair system constitutes an important risk factor in patients with multiple primary cancers, we examined replication errors (RER) at microsatellite loci in 79 primary cancers which had developed among 38 patients with multiple primary cancers. The RER(+) phenotype was observed at five microsatellite loci on chromosomes 2, 3, 11, or 17 in tumors from 34 (89%) of 38 patients with multiple primary cancers but only in 19 tumors from 174 patients (11%) with a single primary cancer. Our results suggested that: (a) genetic instability may play an important role in development of multiple primary cancers, and (b) testing for RER in a primary cancer may be an appropriate approach to detection of patients at high risk for developing multiple primary cancers.

¹ This work was supported in part by the Ministry of Education, Culture and Science, and the Ministry of Health and Welfare of Japan, Research Foundation for Cancer and Cardiovascular Diseases, Osaka, Japan, and the Vehicle Racing Commemorative Foundation.

² To whom requests for reprints should be addressed.

Received 3/29/94. Accepted 5/23/94.

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