The transforming growth factor-β (TGF-β) pathway is important in the growth control of many different cell types, particularly epithelial cells, and is often disrupted in the development of cancer (1 ,2 ). The most common mutation in the TGF-β pathway detected thus far is mutation of the type II receptor (RII) in colon cancers, particularly in tumors with defective mismatch repair or microsatellite instability (MSI) (3 –5 ). These RII mutations occur in a repetitive region of coding sequence, a stretch of 10 adenines, and occur in greater than 90% of colon tumors with MSI (5 ). Frameshift mutations, with insertion or deletion of one or two adenines, result in premature termination of the receptor protein, with loss of the membrane anchor and intracellular kinase domain. This RII mutation also occurs in gastric and endometrial tumors (4 ) and may be a hot spot in other tumor types with microsatellite instability as well.
