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Loss of Heterozygosity Affecting the p53, Rb, and mcc/apc Tumor Suppressor Gene Loci in Dysplastic and Cancerous Ulcerative Colitis¹

Departments of Medicine (GI Division) [B. D. G., J. Y., Y. T., S. J. M.], Microbiology and Immunology [Y. H.], and Pathology [C. N., J. H. R.] and Graduate Program in Molecular and Cell Biology [T. M., S. J. M.], University of Maryland and Lock Raven Veterans Affairs Hospitals, Baltimore, Maryland 21201; Emmanuel College, Cambridge University, Cambridge, England CB2 3AP [V. L. B.]; and Department of Pathology, The Mt. Sinai School of Medicine, New York, New York 10029 [N. H.]

Allelic deletions of tumor suppressor genes have been observed frequently in a variety of human tumors. These losses are believed to contribute to the development of human cancer. Three of the most frequently deleted chromosomal loci contain the tumor suppressor genes p53, retinoblastoma (Rb), and mcc/apc. In order to detect loss of heterozygosity (LOH) within these genes in dysplastic and cancerous ulcerative colitis, we used an application of the polymerase chain reaction. LOH affecting p53 was observed in 8 of 17 (47%) of heterozygous patients, while LOH of Rb and the mcc/apc locus was observed in 9 of 27 (33%) and 13 of 39 (33%) of heterozygotes, respectively. Among 35 patients heterozygous at 2 or more locl, LOH of p53, Rb, and/or mcc/apc was observed in 18 (51%). LOH was more common in left-sided neoplasms. These data suggest that allelic deletion of p53, Rb, mcc, and/or apc is involved in the pathogenesis and/or progression of at least a subset of colonic dysplasias and carcinomas occurring in the setting of ulcerative colitis.

¹ This work was supported by the Crohn's and Colitis Foundation of America, American Cancer Society Grant PDT-419, the Frank C. Bressler Research Fund, a GRA/SRIS award from the University of Maryland Designated Research Initiative Fund, and the Department of Veterans Affairs.

² To whom requests for reprints should be addressed, at Medicine/GI, N3W62, University of Maryland Hospital, 22 South Greene Street, Baltimore, MD 21201.

Received 10/22/91. Accepted 12/ 4/91.

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