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

William M. Grady, Lois L. Myeroff, Sandra E. Swinler, Ashwani Rajput, Sam Thiagalingam, James D. Lutterbaugh, Aaron Neumann, Michael G. Brattain, Jay Chang, Seong Jin Kim, Ken W. Kinzler, Bert Vogelstein, James K.V. Willson, Sanford Markowitz

Research output: Contribution to journalArticle

329 Scopus citations

Abstract

We previously demonstrated that mutational inactivation of transforming growth factor β 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 β signaling blockade distal to RII. The transforming growth factor β pathway and RII in particular are major targets for inactivation in MSS colon cancers as well as in colon cancers with microsatellite instability.

Original languageEnglish (US)
Pages (from-to)320-324
Number of pages5
JournalCancer Research
Volume59
Issue number2
StatePublished - Jan 16 1999
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Grady, W. M., Myeroff, L. L., Swinler, S. E., Rajput, A., Thiagalingam, S., Lutterbaugh, J. D., Neumann, A., Brattain, M. G., Chang, J., Kim, S. J., Kinzler, K. W., Vogelstein, B., Willson, J. K. V., & Markowitz, S. (1999). Mutational inactivation of transforming growth factor β receptor type II in microsatellite stable colon cancers. Cancer Research, 59(2), 320-324.