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

Abstract

We previously demonstrated that mutational inactivation of transforming growth factor beta type II receptors (RIIs) is very common among the 13% of human colon cancers with microsatellite instability. These mutations principally cluster in the BAT-RII polyadenine sequence repeat. Among microsatellite stable (MSS) colon cancers, we now find that non-BAT-RII point mutations inactivate RII in another 15% of cases, thus doubling the known number of colon cancers in which RII mutations are pathogenetic. Functional analysis confirms that these mutations inactivate RII signaling. Moreover, another 55% of MSS colon cancers demonstrate a transforming growth factor beta signaling blockade distal to RII. The transforming growth factor beta pathway and RII in particular are major targets for inactivation in MSS colon cancers as well as in colon cancers with microsatellite instability.

• Authors: W M Grady, L L Myeroff, S E Swinler, A Rajput, S Thiagalingam, J D Lutterbaugh, A Neumann, M G Brattain, J Chang, S J Kim, K W Kinzler, B Vogelstein, J K Willson, S Markowitz
• Journal: Cancer research (Cancer Res) Vol. 59 Issue 2 Pg. 320-4 (Jan 15 1999) ISSN: 0008-5472 [Print] United States
• PMID: 9927040 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Receptors, Transforming Growth Factor beta
• Transforming Growth Factor beta
• Protein Serine-Threonine Kinases
• Receptor, Transforming Growth Factor-beta Type II

Topics

• Adult
• Colonic Neoplasms (genetics)
• Female
• Humans
• Male
• Microsatellite Repeats
• Middle Aged
• Mutation
• Protein Serine-Threonine Kinases
• Receptor, Transforming Growth Factor-beta Type II
• Receptors, Transforming Growth Factor beta (genetics)
• Transforming Growth Factor beta (pharmacology)
• Tumor Cells, Cultured