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.

journal_name

Cancer Res

journal_title

Cancer research

authors

Grady WM,Myeroff LL,Swinler SE,Rajput A,Thiagalingam S,Lutterbaugh JD,Neumann A,Brattain MG,Chang J,Kim SJ,Kinzler KW,Vogelstein B,Willson JK,Markowitz S

subject

Has Abstract

pub_date

1999-01-15 00:00:00

pages

320-4

issue

2

eissn

0008-5472

issn

1538-7445

journal_volume

59

pub_type

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