ABSENCE OF MUTATIONS IN THE ANALYSIS OF CODING SEQUENCES OF THE ENTIRE TRANSFORMING-GROWTH-FACTOR-BETA TYPE-II RECEPTOR GENE IN SPORADIC HUMAN BREAST CANCERS

The transforming growth factor-beta (TGF beta) binds the type II TGF b eta growth factor receptor (TGF beta RII) to inhibit the growth of mos t epithelial tissues. Most human colon and gastric cancers with micros atellite instability (MI) have frameshift mutations in polynucleotide repeats within the TGF beta RII coding region; these mutations truncat e the receptor protein and disable the serine/threonine kinase to prod uce TGF-beta resistance. To further investigate the type, frequency an d tissue distribution of TGF beta RII gene mutations, in this study, w e examined 36 sporadic breast cancers. We previously produced eight in tron based primer pairs for mutational analysis of the entire coding r egion of the TGF beta RII gene. Using these primers, we developed prot ocols for polymerase chain reaction-single strand conformational polym orphism (PCR-SSCP) analysis of PCR products from genomic DNA samples o f 36 breast cancer patients and we tested them for microsatellite inst ability (MI) at eight microsatellite loci. One case demonstrated MI (2 .8%) and we found no mutations. These and other recent data indicate t hat TGF beta RII mutations are essentially confined to colon and gastr ic cancers with MI. The narrow spectrum of tissues containing RII muta tions illustrates the complexity of genetic checkpoints in human carci nogenesis.