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

Abstract
Ulcerative colitis (UC) is a chronic inflammatory disease of the colon associated with a high risk of colorectal cancer. This increased cancer risk is thought to result from the cellular damage induced by the inflammatory field. The aim of this study was to determine the pattern and time course of genomic instability occurring in UC-related neoplasia. Sites of cancer, dysplasia, and nondysplasia from 14 UC colectomy cases containing cancer were analyzed for chromosomal alterations by comparative genomic hybridization (CGH) 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 chromosome 18 or 18q and chromosome 5 or 5q were common in cancer and dysplasia and were occasionally detected in nondysplasia. High-level microsatellite instability was detected in the cancer and dysplasia of two cases. Samples that demonstrated high-level microsatellite instability were unlikely to have chromosomal alterations demonstrable by CGH. These studies suggest that the predominant type of genomic instability in UC-related neoplasia is associated with chromosomal alterations and that this type of genomic instability frequently occurs before the development of histologically defined dysplasia.
AuthorsR F Willenbucher, D E Aust, C G Chang, S J Zelman, L D Ferrell, D H Moore 2nd, F M Waldman
JournalThe American journal of pathology (Am J Pathol) Vol. 154 Issue 6 Pg. 1825-30 (Jun 1999) ISSN: 0002-9440 [Print] United States
PMID10362807 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Topics
  • Adult
  • Aged
  • Cell Transformation, Neoplastic (genetics)
  • Chromosome Aberrations (genetics)
  • Chromosomes, Human, Pair 18 (genetics)
  • Chromosomes, Human, Pair 20 (genetics)
  • Chromosomes, Human, Pair 5 (genetics)
  • Chromosomes, Human, Pair 8 (genetics)
  • Colitis, Ulcerative (complications)
  • Colorectal Neoplasms (complications, genetics)
  • Female
  • Humans
  • Male
  • Microsatellite Repeats (genetics)
  • Middle Aged
  • Nucleic Acid Hybridization
  • Polymerase Chain Reaction
  • Precancerous Conditions (genetics)

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