Mutational inactivation of transforming growth factor beta receptor type II in microsatellite stable colon cancers

We previously demonstrated that mutational inactivation of transforming gro wth factor beta type IT receptors (RIIs) is very common among the 13% of hu man colon cancers with microsatellite instability. These mutations principa lly duster in the BAT-RII polyadenine sequence repeat. Among microsatellite stable (MSS) colon cancers, we now find that non-BAT-RII point mutations i nactivate RII in another 15% of cases, thus doubling the known number of co lon cancers in which RII mutations are pathogenetic, Functional analysis co nfirms that these mutations inactivate RII signaling, Moreover, another 555 of MSS colon cancers demonstrate a transforming growth factor beta signali ng blockade distal to RII, The transforming growth factor beta pathway and RII in particular are major targets for inactivation in MSS colon cancers a s well as in colon cancers with microsatellite instability.