Abstract
The transforming growth factor-β (TGF-β) type II receptor (RII) is a colon cancer suppressor gene that is inactivated by mutation in 90% of human colon cancers arising via the microsatellite instability (MSI) pathway of carcinogenesis. To determine the pathophysiological consequence of RII mutations, we have determined the timing of their onset among 22 MSI human colon adenomas of varying stages. No RII mutations were detected in any early MSI adenoma, including all those with simple tubular or villous histology. The earliest RII mutation detected was in a region of high-grade dysplasia but was absent from the surrounding simple adenoma. Six additional RII mutations were all found in highly progressed adenomas that contained regions of frankly invasive adenocarcinoma. These RII mutations were detected in both the advanced adenomas and their adjacent regions of carcinoma. RII mutation is a late event in MSI adenomas and correlates tightly with progression of these adenomas to cancer.
Footnotes
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↵1 This work was supported by NIH Grants RO1 CA 67409 and RO1 CA 72160, by American Cancer Society Grant FRA-451 (to S. M.), by an Advanced Research Training Award from the American Digestive Health Foundation (to W. M. G.), and by NIH Grants P30 CA 43703 and T32 CA 59366 (to Case Western Reserve University). S. M. is an investigator in the Howard Hughes Medical Institute.
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↵2 To whom requests for reprints should be addressed, at UCRC 2, Room 200, Ireland Cancer Center, 11001 Cedar Road, Cleveland, OH 44106.
- Received March 2, 1998.
- Accepted June 2, 1998.
- ©1998 American Association for Cancer Research.
Volume 58, Issue 14
