P53基因的等位基因缺失早在过去已通过Southern杂交表明高频地在散发性结肠癌和其他多种人类肿瘤中发生。我们考察了患有慢性溃疡性结肠炎、在P53基因外显子4上缺乏编码区第72个密码子多态性、并且患上肿瘤和异型增生的患者中，P53基因等位失的频率。从在该位点上为杂合子的10名患者的肿瘤和异型增生标本的细胞基于DNA含量通过流式细胞术进行分选。从二倍体和非整倍体人群中扩增P53外显子4区域，通过聚合酶链式反应（PCR）并用BstUI酶进行消化。3个淋巴结转移癌，6个异型增生中的4个，和1名不确定是否有异型增生的患者都表现出了P53基因等位性缺失的迹象。为了比较，分析了10例散发性结肠癌病例中的7例表现为P53等位基因缺失。这些结果表明PCR分析，并通过多态性位点的限制性内切酶消化提供了一种迅速而明确的方法来分析结肠粘膜细胞中小量细胞丧失杂合性的损失。这种失调在溃疡性结肠炎之前即会出现，并可能在最早期的病理学可辨认前体阶段存在。

Allelic deletions of the p53 gene previously were demonstrated by Southern hybridization to occur in high frequency in sporadic colon carcinomas and in a variety of other human tumors. We have examined the frequency of allelic loss of the p53 gene in carcinoma and dysplasia arising in patients with chronic ulcerative colitis who are heterozygous for the codon 72 polymorphism in exon 4 of the p53 gene. Cells derived from carcinoma and dysplasia specimens from 10 patients who were heterozygous at this locus were sorted by flow cytometry on the basis of DNA content. The p53 exon 4 region was amplified from diploid and aneuploid populations, via a polymerase chain reaction (PCR), and digested with BstUI. Three of three carcinomas, four of six dysplasias, and one patient who was indefinite for dysplasia demonstrated evidence of allelic loss of the p53 gene. Seven of ten cases of sporadic colon carcinoma, analyzed for comparative purposes, exhibited loss of a p53 allele. These results demonstrate that PCR analysis, followed by restriction endonuclease digestion of a polymorphic locus, can provide a rapid, definitive method for analyzing loss of heterozygosity in small numbers of cells from colonic mucosa. Such loss precedes cancer in ulcerative colitis and can be present in its earliest histologically identifiable precursor.