Description of Project:

Patients with chronic UC have an increased risk of the developing colorectal cancer. The overall objectives of this research are to develop a better understanding of the molecular mechanisms of neoplastic progression in chronic extensive ulcerative colitis (UC) for the earlier, more cost effective diagnosis of curable cancer or its precursors. Throughout this study, we have demonstrated that UC patients with dysplasia/cancer had substantial genomic instability in both their dysplastic and nondysplastic colonic mucosa, while instability was not present in the UC patients without dysplasia/cancer. These results suggest that UC patients who develop dysplasia or cancer have an underlying process of genomic instability in their colonic mucosa while UC patients who are dysplasia-free do not. The finding of widespread genomic instability in UC patients with neoplasia is important for several reasons:

1. it sheds light on the underlying mechanism of UC tumorigenesis-one of a mutator phenotype.
2. It may provide a molecular marker for patients who have neoplasia or might develop it in the future-offering a needed adjunct to histologic-based surveillance.
3. It opens the door to address new key questions, such as why it is that some UC patients have a mutator phenotype, while others do not.