MUTATION ANALYSIS OF CODING SEQUENCES OF THE ENTIRE TRANSFORMING GROWTH-FACTOR-BETA TYPE-II RECEPTOR GENE IN SPORADIC HUMAN COLON-CANCER USING GENOMIC DNA AND INTRON PRIMERS

Mutations in the transforming growth factor beta type II receptor (TGF beta RII) gene have been detected in several human cancers exhibiting microsatellite instability. To extend analyses of this gene, we previ ously investigated the exon-intron organization of the TGF beta RII. g ene and defined seven exons and flanking intron sequences. In this stu dy, we further determined the nucleotide sequences surrounding these s even exons and designed eight sets of intron-based primers to examine the entire coding region of the TGF beta RII gene. Using these primers , we screened genomic DNA sequences from 30 sporadic colorectal cancer s for mutations of the TGF beta RII. gene. TGF beta RII mutations were detected in two of 30 tumors and both displayed microsatellite instab ility. One had a deletion in a polyadenine tract in exon 3 and the oth er had a point mutation in the kinase domain located in exon 7. There were no mutations in exons 1, 2, 4, 5 and 6. These results further imp licate the polyadenine tract and kinase domain as mutational hotspots in the TGF beta RII gene in cells,vith genomic instability and suggest that TGF beta RII gene mutations occur rarely in cells lacking genomi c instability.