DNA fingerprinting abnormalities can distinguish ulcerative colitis patients with dysplasia and cancer from those who are dysplasia/cancer-free.
Patients with extensive ulcerative colitis (UC) of longer than 8 years duration are at high risk for the development of colorectal cancer. The cancers in these patients appear to develop in a stepwise manner with progressive histological changes from negative for dysplasia --> indefinite for dysplasia --> dysplasia --> cancer. The aim of this study was to determine the timing and extent of genomic instability in the progression of UC dysplasia and cancer. Using two polymerase chain reaction (PCR)-based DNA fingerprinting methods, arbitrarily primed PCR and intersimple sequence repeat PCR, we assessed DNA sequence variation in biopsies across the spectrum of cancerous, dysplastic, and nondysplastic mucosa. UC patients with dysplasia/cancer had substantial genomic instability in both their dysplastic and nondysplastic colonic mucosa, whereas instability was not present in the majority of UC patients without dysplasia/cancer. The degree of instability in nondysplastic tissue was similar to that of dysplastic/cancerous mucosa from the same patient, suggesting that this instability was widespread and reached the maximum level early in neoplastic progression. These results suggest that UC patients who develop dysplasia or cancer have an underlying process of genomic instability in their colonic mucosa whereas UC patients who are dysplasia-free do not.
Chen
Ru
R
Departments of Pathology, Biostatistics, and Medicine, University of Washington, Seattle, Washington 98195, USA.
Rabinovitch
Peter S
PS
Crispin
David A
DA
Emond
Mary J
MJ
Koprowicz
Kent M
KM
Bronner
Mary P
MP
Brentnall
Teresa A
TA
D001706:Biopsy; D003093:Colitis, Ulcerative / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D003110:Colonic Neoplasms / Q000175:diagnosis / Q000209:etiology / Q000235:genetics* / Q000473:pathology*; D004247:DNA / Q000235:genetics*; D016172:DNA Fingerprinting / Q000379:methods*; D017931:DNA Primers; D003937:Diagnosis, Differential; D018450:Disease Progression; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology; D016133:Polymerase Chain Reaction / Q000379:methods; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D017931:DNA Primers; D004247:DNA