MUTATIONS IN THE P53 GENE - AN EARLY MARKER OF NEOPLASTIC PROGRESSION IN ULCERATIVE-COLITIS
MUTATIONS IN THE P53 GENE - AN EARLY MARKER OF NEOPLASTIC PROGRESSION IN ULCERATIVE-COLITIS
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DOI：
10.1016/0016-5085(94)90161-9
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发表时间：
1994-08-01
期刊：
影响因子：
29.4
通讯作者：
BURMER, GC
中科院分区：
文献类型：
--
作者：
BRENTNALL, TA;CRISPIN, DA;BURMER, GC
背景/目的：在长期广泛的溃疡性结肠炎中，在组织学向癌的进展过程中，非整倍体发生较早，p53杂合性丢失（p53 LOH）发生较晚。方法：我们建立了一种快速、敏感的p53基因248位密码子突变筛查方法。该p53突变的地理分布在两个248密码子突变的新鲜结肠切除术标本（1例癌，1例异型增生）中进行了定位，并与克隆扩张、组织学进展和等位基因丢失模式相关。结果：p53突变与组织学分级高度相关，且p53 LOH的分布范围较p53 LOH更广。结论：这些发现表明p53突变是先于p53 LOH的早期遗传事件。p53突变与非整倍体的密切相关性（P> 0.0001）强调了正常p53在G1检查点的作用，以帮助防止遗传损伤的细胞进入细胞周期。
Background/Aims:In long-term extensive ulcerative colitis, aneuploidy occurs earlier and loss of heterozygosity forp53(p53LOH) later during histological progression towards carcinoma. This study determined the time of onset ofp53mutation in this progression.Methods:We developed a rapid, sensitive screening assay forp53mutations at codon 248. The geographic distribution of thisp53mutation was mapped in two fresh colectomy specimens with mutations of codon 248 (1 cancer, 1 dysplasia) and correlated with patterns of clonal expansion, histological progression, and allelic loss. Numerous samples from throughout both colons were analyzed (216 for histology, 142 for DNA content, 104 for mutation, and 41 forp53LOH).Results: p53mutation correlated highly with histological grade and was distributed more extensively thanp53LOH. Mutation, but not LOH, was also found in diploid, nondysplastic colonic mucosa adjacent to dysplastic areas.Conclusions:These findings suggest thatp53mutation appears to be an early genetic event that precedesp53LOH. The very close correlation ofp53mutation with aneuploidy (P> 0.0001) emphasizes the role of normalp53at the G1checkpoint to help prevent entry of genetically damaged cells into the cell cycle.