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

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

Simmons Comprehensive Cancer Center

Research output: Contribution to journal › Article › peer-review

353 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 language	English (US)
Pages (from-to)	320-324
Number of pages	5
Journal	Cancer research
Volume	59
Issue number	2
State	Published - Jan 16 1999

ASJC Scopus subject areas

Oncology
Cancer Research

Cite this

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.

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title = "Mutational inactivation of transforming growth factor β receptor type II in microsatellite stable colon cancers",

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.",

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

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AU - Grady, William M.

AU - Myeroff, Lois L.

AU - Swinler, Sandra E.

AU - Rajput, Ashwani

AU - Thiagalingam, Sam

AU - Lutterbaugh, James D.

AU - Neumann, Aaron

AU - Brattain, Michael G.

AU - Chang, Jay

AU - Kim, Seong Jin

AU - Kinzler, Ken W.

AU - Vogelstein, Bert

AU - Willson, James K V

AU - Markowitz, Sanford

PY - 1999/1/16

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N2 - 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.

AB - 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.

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

Abstract

ASJC Scopus subject areas

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