Molecular screening of patients with long standing extensive ulcerative colitis: detection of p53 and Ki-ras mutations by single strand conformation polymorphism analysis and differential hybridisation in colonic lavage fluid. Issue 6 (1st June 1999)

• Record Type: Journal Article
• Authors: Lang, S M; Stratakis, D F; Heinzlmann, M; Heldwein, W; Wiebecke, B; Loeschke, K
• Is Part Of: Gut. Volume 44:Issue 6(1999)
• Page Start: 822
• Page End: 825
• Publication Date: 1999-06-01
• Subjects: p53 -- K-ras -- colonic lavage -- ulcerative colitis -- molecular screening; Gastroenterology -- Periodicals; 616.33
• DOI: 10.1136/gut.44.6.822
• Languages: English
• ISSNs: 0017-5749

Abstract

Abstract : BACKGROUND: In patients with long standing ulcerative colitis at risk of developing malignancy, mutations of the p53 and Ki- ras gene were investigated in lavage solution obtained at surveillance colonoscopy. METHODS: DNA was isolated from 31 consecutive patients with total or subtotal ulcerative colitis and a disease duration of between seven and 26 years. Twenty seven control patients showed no macroscopic or microscopic inflammation on colonoscopy. Exons 5–8 of the p53 gene and exon 1 of the Ki- ras gene were amplified by polymerase chain reaction. Mutations of the p53 gene were detected by single strand conformation polymorphism analysis. Point mutations of the Ki- ras gene were hybridised on dot blots with oligonucleotides marked with digoxigenin. RESULTS: In all cases of ulcerative colitis and in all of the 27 control patients, wild type p53 and wild type Ki- ras could be detected. In four patients with ulcerative colitis, a mutation in exon 5 to 7 of the p53 gene was found, and two patients had a mutation of the Ki- ras gene (Gly to Asp-12, Gly to Val-12). None of these patients had dysplasia in serial biopsy specimens, and all but one had had the disease for more than 10 years. One control patient had a mutation. CONCLUSIONS: Mutations were more frequent in patients with long standing ulcerative colitis (19%) than in control patients (3%, p = 0.07). The technique may be useful for screening for early malignancy in ulcerative colitis.