ASSOCIATION OF P53 MUTATIONS WITH SHORT SURVIVAL IN COLORECTAL-CANCER
ASSOCIATION OF P53 MUTATIONS WITH SHORT SURVIVAL IN COLORECTAL-CANCER
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DOI：
10.1016/s0016-5085(94)94217-x
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发表时间：
1994-01-01
期刊：
影响因子：
29.4
通讯作者：
THOMAS, G
中科院分区：
文献类型：
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作者：
HAMELIN, R;LAURENTPUIG, P;THOMAS, G
p53基因是位于染色体17 p上的一种肿瘤抑制基因，其突变是人类肿瘤中最常见的遗传学改变。细胞内p53浓度的增加，这是经常，但不是系统地与p53突变，已被提出与一些肿瘤类型的预后不良。在结直肠癌中，这种意义仍然是一个有争议的问题。为了直接探讨预后和p53突变之间的关系，本研究筛选了一系列85例大肠癌的突变，该基因的外显子5-8。MethodsPolymerase chain reaction扩增产物从肿瘤DNA进行了分析，变性梯度凝胶电泳和直接DNA测序。观察到突变的存在与短生存期之间存在强相关性（P= 0.003）。当肿瘤根据其组织学分期进行分类时，多变量考克斯模型分析显示，p53突变，而不是17 p等位基因丢失（以前提出传达预后信息），被保留为唯一的独立预后因素（相对风险，2.25; 95%置信区间，1.06-4.80;P< 0.029）。结论结合分期，直接监测p53突变可提高结直肠癌的预后准确性。
Background/AimsMutations in p53, a tumor suppressor gene located on chromosome 17p, are the most frequent genetic alterations found in human cancers. Increased intracellular concentration of p53, which is frequently but not systematically related to p53 mutation, has been proposed to be associated with poor prognosis in some tumor types. In colorectal cancer, this significance is still a matter of debate. To directly investigate the relationship between prognosis and p53 mutation, this study screened a series of 85 colorectal carcinomas for mutations in exons 5–8 of this gene.MethodsPolymerase chain reaction-amplified products from tumor DNA were analyzed by denaturing gradient gel electrophoresis and direct DNA sequencing.ResultsForty-four tumors were found to be mutated (52%). A strong correlation between the presence of a mutation and short survival was observed (P= 0.003). When tumors were classified according to their histological stage, a multivariate Cox model analysis showed that p53 mutation, rather than 17p allelic loss (previously proposed to convey prognostic information), was retained as the only independent prognostic factor (relative risk, 2.25; 95% confidence interval, 1.06–4.80;P< 0.029).ConclusionsCombined with staging, direct monitoring of p53 mutation improves prognostic accuracy for colorectal cancer.