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[Cancer Research 55, 5548-5550, December 1, 1995]
© 1995 American Association for Cancer Research
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Microsatellite Instability and Mutations of the Transforming Growth Factor ß Type II Receptor Gene in Colorectal Cancer1

Ramon Parsons, Lois L. Myeroff, Bo Liu, James K. V. Willson, Sanford D. Markowitz2, Kenneth W. Kinzler and Bert Vogelstein

Johns Hopkins Oncology Center, Baltimore, Maryland 21231 [R. P., B. L., K. W. K., B. V.]; Department of Medicine and Ireland Cancer Center, University Hospitals of Cleveland and Case Western Reserve University, Cleveland, Ohio 44106 [L. L. M., J. K. V. W., S. D. M.], and Howard Hughes Medical Institute, Chevy Chase, Maryland 20815 [B. V.]

The TGFß type II receptor (RII) was found to be mutated within a polyadenine tract in 100 of 111 (90%) colorectal cancers with microsatellite instability. Other polyadenine tracts of similar length were mutated in these samples but not as frequently as RII. In most cases, the polyadenine tract mutations affected both alleles of RII, and in four tumors heterozygous for the polyadenine mutations, three had additional mutations that were expected to inactivate the other RII allele. These genetic data support the idea that RII behaves like a tumor suppressor during CR cancer development and is a critical target of inactivation in mismatch repair-deficient tumors.

1 This work was supported by NIH Grants CA09320, CA35494, CA51183, CA57208, and CA62924, American Cancer Society Grant FRA-451, and the Clayton Fund. B. V. is an investigator of the Howard Hughes Medical Institute.

2 To whom requests for reprints should be addressed, at Ireland Cancer Center, University Circle Research Center 2, Room 200, 11001 Cedar Road, Cleveland, OH 44106.

Received 10/ 6/95. Accepted 10/25/95.




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