Thorlacius S, Börresen A L, Eyfjörd J E
Molecular and Cell Biology Research Laboratory, Icelandic Cancer Society, Reykjavik.
Cancer Res. 1993 Apr 1;53(7):1637-41.
Mutations in the p53 gene are among the most common genetic changes in human carcinomas. They have been found in many tumor types including colon, lung, and breast. We have used constant denaturant gel electrophoresis in order to screen samples from 109 breast carcinomas for mutations in four conserved regions, exons 5, 7, and 8, of the p53 gene. Samples were also analyzed for allelic loss of the p53 gene and of markers more distal on chromosome 17 p. Mutations were confirmed by DNA sequencing. Mutations were found in 18 of the 109 samples (16.5%). Loss of heterozygosity at 17p was detected in the majority of informative mutated cases. All cases were also screened for germ line mutations, but none were found. The results obtained were analyzed with respect to clinical parameters and prognosis. There was a significant association between p53 mutation and low content of estrogen receptor protein in the tumors (P = 0.01). An association with poor prognosis was strongly indicated by mortality rates that were 37.5% among the patients with p53 mutation and 9.4% for the control group (mean follow up, 32 months). P53 mutation was found to be the strongest negative factor against survival in a covariate survival analysis (P = 0.001).
p53基因的突变是人类癌症中最常见的基因变化之一。它们在包括结肠癌、肺癌和乳腺癌在内的多种肿瘤类型中都有发现。我们使用恒定变性剂凝胶电泳来筛查109例乳腺癌样本中p53基因四个保守区域（外显子5、7和8）的突变情况。还对样本进行了p53基因以及17号染色体短臂上更远端标记的等位基因缺失分析。通过DNA测序确认突变。在109个样本中有18个（16.5%）发现了突变。在大多数有信息的突变病例中检测到17p杂合性缺失。所有病例也都筛查了种系突变，但未发现。根据临床参数和预后对所得结果进行了分析。p53突变与肿瘤中雌激素受体蛋白含量低之间存在显著关联（P = 0.01）。p53突变患者的死亡率为37.5%，而对照组为9.4%（平均随访32个月），这强烈表明与预后不良有关。在协变量生存分析中，p53突变被发现是影响生存的最强负面因素（P = 0.001）。
