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6th ESACP Congress, Heidelberg, April 7-11, 1999 |
A016
The gastrointestinal tract offers unusual opportunities for the study of
early genetic alterations leading to neoplasia. In both Ulcerative Colitis
(UC) and Barrett's esophagus we have studied endoscopic biopsies from
patients who are at high risk of progression to cancer. In UC flow cytometry
was useful to document that DNA aneuploidy, an indicator of genomic
instability and clonal expansion, precedes and surrounds regions of
dysplasia in the colon. Comparative genomic hybridization (CGH) showed the
presence of even larger regions of chromosomal instability in DNA diploid
tissue. Fluorescence in situ hybridization (FISH) is the most sensitive of
all, and shows that chromosomal instability (CIN) is present throughout the
colon of patients that have progressed to focal dysplasia or cancer, but is
not present in non-progressors. CIN is not always clonal and involves some
chromosomes more than others. One intriguing hypothesis is that CIN in UC is
related to shortened telomeres. In Barrett's esophagus flow cytometry has
also shown genomic instability and clonal expansion. Sorted epithelial cells
from patients with Barrett's esophagus followed prospectively have been used
to characterize the sequence and patterns of loss of heterozygosity during
neoplastic evolution.
GENOMIC INSTABILITY IN GASTROINTESTINAL MODELS OF NEOPLASTIC PROGRESSION
Rabinovitch PS
Dept. of Pathology, University of Washington, Seattle, Washington, USA.