GENOMIC STRUCTURE OF THE TRANSFORMING GROWTH-FACTOR-BETA TYPE-II RECEPTOR GENE AND ITS MUTATIONS IN HEREDITARY NONPOLYPOSIS COLORECTAL CANCERS

To characterize the tumorigenetic role of the transforming growth fact or beta 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 colorec tal cancer patients were analyzed for mutations in the entire coding r egion. 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 inactivatio n mechanism with tumor suppressor genes and that mutations of it may o ccur in the early stage of tumorigenesis.