食管癌前病变P53肿瘤抑制基因突变分析

利用聚合酶链反应－单链构型－ＤＮＡ序列测定技术对食管癌高发区河南辉县和林县居民食管癌前病变和癌组织进行Ｐ５３肿瘤抑制基因第５，６，７和８外显子突变分析。在３７例非癌患者活检组织中共发现８例突变。其中１例发生在正常上皮，３例发生在基底细胞增生，４例发生在间变。突变均发生在第５外显子。３例在１７５密码子，２例在１７６密码子，其余３例分别在１５９，１３２和１３５密码子，２９例鳞癌组织检查发现１６例Ｐ５３基因突变（５５％）。突变多分布在第５和７外显子。点突变中，７５％为碱基转换，２５％为碱基颠换。结果提示Ｐ５３基因突变在食管癌的早期阶段已发生。

Molecular pathological studies on the esophageal precancerous lesions: Analysis of P53 mutation

P53 gene mutation in exons of 5, 6, 7 and 8 were analyzed with PCR-SSCP-DNA sequencing method on the esophageal precancerous and cancerous lesions from subjects in a high incidence area, Huixian County of Henan Province. Among the 37 biopsy samples showing accumulation of P53 protein in immunohistochemical staining, eight cases were found with P53 mutation. Missense mutations of P53 gene were detected in 1 normal,3 hyperplasia and 4 dysplasia epithelia and all mutations occurred at exon 5 with 3 at codon 175, 2 at codon 176, 1 each at codon 159, 135 and 132. Among 29 esophageal squamous cell carcinoma, mutations were dtetcted in 16 (55%). Most of the mutations were located at either exon 5 or 7. Twelve samples contained different missense point mutations with 75% transitions and 25% transversions. The results demonstrate that P53 protein accumulation and gene mutation may occur at very early stages of esophageal carcinogenesis.