title: Loss of heterozygosity and microsatellite instability in non-neoplastic mucosa from patients with chronic ulcerative colitis.
abstract: Microsatellite instability and allelic deletions of tumor suppressor genes have been observed frequently in tumors. Molecular pathogenesis of the development of dysplasia and carcinoma in ulcerative colitis is still unclear. In order to detect microsatellite alterations in ulcerative colitis, we analyzed loss of heterozygosity (LOH) and microsatellite instability (MI) on chromosomes 3, 6, 7, 12, and tumor suppressor gene loci, including p53, APC, and p16, of chronically inflamed, non-dysplastic epithelium after microdissection. Twelve of 13 (92%) cases showed 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, LOH at p53 and p16 was detected in only one case each. These results suggest that chronic inflammation may initiate microsatellite alteration, which subsequently transform ulcerative colitis to dysplasia or cancer. This finding provides information for the evaluation and treatment of patients with ulcerative colitis.
authors.affiliation: Department of Pathology, National Institutes of Health, Bethesda, MD, USA.
authors.initials: WS
authors.lastname: Park
authors.initials: T
authors.lastname: Pham
authors.initials: C
authors.lastname: Wang
authors.initials: S
authors.lastname: Pack
authors.initials: E
authors.lastname: Mueller
authors.initials: J
authors.lastname: Mueller
authors.initials: A
authors.lastname: Vortmeyer
authors.initials: Z
authors.lastname: Zhuang
authors.initials: F
authors.lastname: Fogt