FREQUENT LOSS OF A P53 ALLELE IN CARCINOMAS AND THEIR PRECURSORS IN ULCERATIVE-COLITIS
FREQUENT LOSS OF A P53 ALLELE IN CARCINOMAS AND THEIR PRECURSORS IN ULCERATIVE-COLITIS
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DOI：
10.3727/095535491820873254
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发表时间：
1991-01-01
影响因子：
16.2
通讯作者：
RABINOVITCH, PS
中科院分区：
文献类型：
--
作者：
BURMER, GC;CRISPIN, DA;RABINOVITCH, PS
p53基因的等位基因缺失先前通过Southern杂交证明在散发性结肠癌和其他多种人类肿瘤中发生的频率很高。我们研究了p53基因4外显子密码子72多态性杂合的慢性溃疡性结肠炎患者中p53基因等位基因丢失的频率。采用流式细胞术对10例在该位点杂合的癌和非典型增生患者的细胞进行分选。通过聚合酶链反应（PCR）从二倍体和非整倍体群体中扩增出p53外显子4区，并用BstUI酶切。3例癌中的3例，6例发育不良中的4例，1例发育不良的患者表现出p53基因等位基因缺失的证据。10例散发性结肠癌中有7例表现出p53等位基因的缺失。这些结果表明，PCR分析，然后用限制性内切酶对多态性位点进行酶切，可以提供一种快速、确定的方法来分析结肠粘膜中少量细胞的杂合性缺失。在溃疡性结肠炎中，这种丧失先于癌症发生，并可在其最早的组织学可识别的前体中出现。
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.