Comparative genomic hybridization analysis of chromosomal alterations in patients with long-standing ulcerative colitis

Patients with ulcerative colitis (UC) are prone to develop colorectal cance r which is related to the duration and extent of the disease. One of the ea rliest events in tumor progression is the development of aneuploidy. Aneupl oidy is correlated with the grade of dysplasia which serves as a common but not always reproducible marker for the prediction of UC associated formati on of cancer. We analyzed 48 biopsy samples from 5 patients with long-stand ing ulcerative colitis by comparative genomic hybridization (CGH). The majo rity of these samples represented premalignant stages which are not well ch aracterized at the molecular level as yet. We compared biopsy samples from different colon locations in regard to chromosomal alterations, dysplasia s tatus and DNA index. Besides chromosomal changes occurring only in certain patients in restricted areas of the colon we also detected amplifications a nd deletions which were common in all persons throughout the colon. The sta ge of dysplasia seems to have no influence on the number and appearance of chromosomal changes. Amplifications in 2, 3, 6, 9, 11, 12 and 15 were found in almost all cases. In dysplastic samples chromosomal regions 3, 6 and I I revealed gains of DNA. Deletions were detected within 8q, 15, 18q, 20p an d 22q. The affected chromosomal regions may contain yet unknown oncogenes o r tumor suppressor genes participating in UC associated carcinogenesis. The conspicuous regions found in the CGH experiments allow the selective and d etailed characterization at a molecular level.