LOSS OF HETEROZYGOSITY AND MICROSATELLITE INSTABILITY IN NONNEOPLASTIC MUCOSA FROM PATIENTS WITH CHRONIC ULCERATIVE-COLITIS

Microsatellite instability and allelic deletions of tumor suppressor g enes have been observed frequently in tumors. Molecular pathogenesis o f the development of dysplasia and carcinoma in ulcerative colitis is still unclear. In order to detect microsatellite alterations in ulcera tive colitis, we analyzed loss of heterozygosity (LOH) and microsatell ite instability (MI) on chromosomes 3, 6, 7, 12, and tumor suppressor gene loci, including p53, APC, and p16, of chronically inflamed, non-d ysplastic epithelium after microdissection. Twelve of 13 (92%) cases s howed LOH and/or MI at one or more loci. LOH at chromosome 3 and MI at chromosome 12 were observed in 50% and 62%, respectively. However, LO H at p53 and p16 was detected in only one case each. These results sug gest that chronic inflammation may initiate microsatellite alteration, which subsequently transform ulcerative colitis to dysplasia or cance r. This finding provides information for the evaluation and treatment of patients with ulcerative colitis.