p53基因突变与食管癌生物学行为的关系  

THE RELATIONSHIP BETWEEN p53 MUTATION AND ESOPHAGEAL CANCER BIOLOGICAL BEHAVIOR

作　　者：何友吉[1] 李明发[1] 单祥年[1] 

机构地区：[1]南京铁道医学院生物教研室

出　　处：《中华医学遗传学杂志》1998年第1期1-4,共4页Chinese Journal of Medical Genetics

基　　金：江苏自然科学基金;江苏省教委优秀青年教师基金

摘　　要：目的为了探讨ｐ５３基因突变与食管癌生物学行为及预后的关系。方法应用ＰＣＲ－ＳＳＣＰ结合ＤＮＡ直接银染测序，对３０例散发性食管癌组织ｐ５３基因第５～８外显子进行检测。结果检出１１例阳性，突变检出率为３６．７％。９例为点突变，其中错义突变４例、无义突变２例、同义突变３例，其余２例为碱基插入和缺失导致的移码突变。统计学分析显示：中低分化食管癌的ｐ５３突变率为５６．３％，高分化组为１４．３％，两组相比有非常显著性差异（Ｐ＝０．０２５）；癌组织浸润累及食管壁全层的ｐ５３突变率５２．６％显著高于未累及全层组９．１％（Ｐ＝０．０２４）；有淋巴结转移组与无淋巴结转移组相比，ｐ５３突变率分别为６１．５％和１７．６％也具有非常显著性差异（Ｐ＝０．０２４）。结论ｐ５３基因突变与食管癌多种生物学行为如组织分化程度、肿瘤浸润程度及淋巴结转移有明显相关性。因此检测食管癌组织中是否存在ｐ５３基因突变有助于判断食管癌的恶性程度和患者的预后。还讨论了ｐ５３基因的“显性负效应”及同义突变的遗传学效应。Objective To investigate the relationship between p53 mutation and esophageal cancer biological behavior as well as its prognostic role in esophageal cancer. Method Mutations in exon 5-8 of p53 were screened in 30 sporadic esophageal cancers by a combination of PCR SSCP and PCR direct DNA silver sequencing. Results Mutations were found in 11 cases (36.7%). There were 9 point mutations, including 4 missense mutations, 2 nonsense mutations, 3 silent mutations. The other 2 cases were frameshift mutations due to base insertion and deletion. With statistical analysis, the p53 mutation rate was 56.3% in moderately and poorly differentiated esophageal cancers, 14.3% in well differentiated cases, with a highly significant difference between the two groups ( P =0 025). The mutation rate of the cancers with all layers invaded (52.6%) was remarkably higher than that of the cancers without all layers invaded (9.1%)( P =0 024). A significantly higher rate of p53 mutation was also seen in cases with lymph nodes metastasis (61.5%) than in cases with no lymph nodes metastasis (17.6%)( P =0 024).Conclusion The data suggest that there is a strong correlation between the presence of p53 mutation and the biological behavior of human esophageal cancer, such as histologic differentiation, invasion stage, and regional lymph nodes metastasis. Detection of p53 mutation can be helpful in identifying more progressive esophageal cancer and assessing prognosis. The study also discussed the dominant negative effect of p53 and the genetic effect of silent mutation

关 键 词：食管肿瘤 P53基因 基因突变 生物学行为 

分 类 号：R735.1[医药卫生—肿瘤]