The short adenine repeat in the coding sequence of TGF-beta receptor II (TGFBR2) gene is frequently targeted by loss-of-function frameshift mutations in colon cancers with microsatellite instability (MSI). The 1- or 2-bp deletions in the adenine stretch of TGFBR2 cDNA introduce a premature stop codon that leads to degradation of the majority of mutant transcripts through nonsense-mediated decay or to production of a truncated TGFBR2 that cannot be presented on the cell surface. Cells that harbor TGFBR2 MSI frameshift mutations are resistant to TGF-beta (TGFB1)-mediated growth inhibition.