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Chromosomal alterations in ulcerative colitis-related neoplastic progression
R F Willenbucher1, S J Zelman, L D Ferrell
1Cancer Center, University of California, San Francisco, USA.
Gastroenterology
|September 1, 1997
Summary
Genomic changes, including chromosomal alterations, may occur before dysplasia develops in ulcerative colitis (UC) cancer progression. Early detection of these changes could help identify high-risk patients.
Area of Science:
- Genomic instability in colorectal cancer
- Molecular pathology of inflammatory bowel disease
Background:
- Ulcerative colitis (UC) is a risk factor for colorectal cancer.
- The timing of genomic derangement relative to dysplasia in UC-related neoplasia is not well understood.
Purpose of the Study:
- To investigate if chromosomal alterations precede histological dysplasia in UC-related neoplastic progression.
- To identify early molecular events in UC-associated colorectal cancer development.
Main Methods:
- Fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH) were used.
- Analysis was performed on DNA from cancer, dysplasia, and nondysplastic epithelium in UC colectomy specimens.
- Pericentromeric probes were utilized to assess chromosome copy number alterations.
Main Results:
- Significant chromosomal copy number alterations were observed in cancer, dysplasia, and nondysplastic UC epithelium.
- Clonal chromosomal losses and gains were detected in most dysplasia and cancer sites.
- Relative loss of chromosome 18 was frequently observed.
Conclusions:
- Chromosomal alterations appear to occur early in UC-related neoplasia, potentially preceding dysplasia.
- Loss of 18q may play a role in UC-associated colorectal cancer progression.
- Detecting chromosomal alterations could aid in identifying patients at high risk for colorectal cancer.
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