title: Hypermethylation of the p16INK4a promoter in colectomy specimens of patients with long-standing and extensive ulcerative colitis.
abstract: Functional inactivation of the p16INK4a gene has been reported to be involved in the development of a variety of human malignancies. Recent evidence shows that transcriptional silencing as a consequence of hypermethylation of CpG islands is the predominant mechanism of p16INK4a gene inactivation in sporadic colon cancer. This study sought to identify the significance of p16INK4a methylation in the colonic epithelium of patients with long-standing ulcerative colitis. A total of 89 tissue samples was retrieved from three colectomy specimens. A methylation-specific PCR assay was applied. The methylation status was compared with histological findings and the flow cytometrically determined DNA index. Hypermethylation of the p16INK4a promoter region was detected in 12.7% of samples that were negative for dysplasia. However, 70.0% of samples with dysplasia and all of the samples with carcinomatous lesions revealed hypermethylation. Hypermethylation of the p16INK4a gene promoter was detected already in 40% of specimens with lesions indefinite for dysplasia and in 13.7% of samples with exclusively diploid cell populations. These results suggest that hypermethylation of the p16INK4a promoter region is a frequent and early occurring event during the process of neoplastic progression in ulcerative colitis.
authors.affiliation: Department of Internal Medicine I, University of Tuebingen, Germany.
authors.forename: C J
authors.initials: CJ
authors.lastname: Hsieh
authors.forename: B
authors.initials: B
authors.lastname: Klump
authors.forename: K
authors.initials: K
authors.lastname: Holzmann
authors.forename: F
authors.initials: F
authors.lastname: Borchard
authors.forename: M
authors.initials: M
authors.lastname: Gregor
authors.forename: R
authors.initials: R
authors.lastname: Porschen
mesh_terms: D003082:Colectomy; D003093:Colitis, Ulcerative / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D019175:DNA Methylation; D006801:Humans; D011379:Prognosis; D011401:Promoter Regions, Genetic
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16