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Genomic Structure of the Transforming Growth Factor ß Type II Receptor Gene and Its Mutations in Hereditary Nonpolyposis Colorectal Cancers¹

Department of Hygiene and Oncology, Tokyo Medical and Dental University School of Medicine, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113 [S-L. L., W-C.Z. Y.A., Y.Y.], and Department of Surgery, Hoshi General Hospital, 2-1-16 Daimachi, Koriyama, Fukushima 963 [T. N.], Japan

To characterize the tumorigenetic role of the transforming growth factor ß type II receptor (RII) gene, we defined its genomic structure, which consists of seven exons. The sequences of exon-intron junctions were determined to facilitate mutation analysis of each exon. Twenty-five carcinomas and five adenomas from hereditary nonpolyposis colorectal cancer patients were analyzed for mutations in the entire coding region. Four missense mutations (two in adenomas and two in carcinomas) were found in the 10 cases carrying the polyadenine deletions in one allele. These results indicate that RII shares the two-hit inactivation mechanism with tumor suppressor genes and that mutations of it may occur in the early stage of tumorigenesis.

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 (Y. Y.) and by a grant from the Mitsui Life Social Welfare Foundation (Y. Y.).

² To whom requests for reprints should be addressed.

Received 7/26/96. Accepted 8/29/96.

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