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 Resjournal_title
Cancer researchauthors
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 Ssubject
Has Abstractpub_date
1999-01-15 00:00:00pages
320-4issue
2eissn
0008-5472issn
1538-7445journal_volume
59pub_type
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