Genomic instability is an early event during the progression pathway of ulcerative-colitis-related neoplasia

Ulcerative colitis (UC) is a chronic inflammatory disease of the colon asso ciated with a high risk of colorectal cancer. This increased cancer risk is thought to result from the cellular damage induced by the inflammatory fie ld, The aim of this study was to determine the pattern and time course of g enomic instability occurring in UC-related neoplasia. Sites of cancer, dysp lasia, and nondysplasia from 14 UC colectomy cases containing cancer were a nalyzed for chromosomal alterations by comparative genomic hybridization (C GH) and for microsatellite instability using a series of 10 microsatellite markers. Clonal chromosomal alterations were present in 85% of cancer sites , 86% of dysplasia sites, and 36% of nondysplasia sites. Losses of chromoso me 18 or 18q and chromosome 5 or 5q were common in cancer and dysplasia and were occasionally detected in nondysplasia. High-level microsatellite inst ability was detected in the cancer and dysplasia of two cases. Samples that demonstrated high-level microsatellite instability were unlikely to have c hromosomal alterations demonstrable by CGH. These studies suggest that the predominant type of genomic instability in UC-related neoplasia is associat ed with chromosomal alterations and that this type of genomic instability f requently occurs before the development of histologically defined dysplasia .