Infrequent p53 gene alterations in ulcerative colitis

The purpose of this study was to determine whether point mutations and loss of the p53 gene take place in ulcerative colitis which is histologically n egative for dysplasia. DNA was extracted from 13 frozen rectal or colon bio psies and blood samples. Ulcerative colitis was classified histologically a s active (10 cases) and inactive (3 cases). Exons 5-8 were amplified by PCR , treated with exonuclease and shrimp alkaline phosphatase and sequenced by the dideoxy chain termination method with the Sequenase Version 2.0 DNA se quencing kit. PCR products of intron 6 and exon 4 were digested with MspI a nd AccII, respectively, for RFLP analysis. No p53 gene mutation was detecte d in these cases. The number of informative patients for loss of heterozygo sity (LOH) at the p53 intron 6 was high, 11 out of 12 (92%), whereas no LOH was observed. LOH affecting p53 exon 4 was not detected in lesions from 5 of 12 patients (42%). In ulcerative colitis, tumor progression is similar t o that in sporadic colon cancer, and other oncogenes and tumor suppressor g enes are likely to be mutated before the p53 gene.