DCC基因201密码子突变与胃癌相关性的研究

Correlation Between the Mutation of the DCC Gene Codon 201 and Gastric Cancer.

目的 :研究胃癌组织中是否存在大肠癌缺失 (deletedincolorectalcancer,DCC)基因 2 0 1密码子点突变及其与胃癌临床病理因素的相关性。方法 :取 5 4例胃癌病人的胃癌组织和癌旁黏膜组织及非胃癌病人的正常胃黏膜组织标本 30份 ,行PCR +限制性片段长度多态性 (restrictionfragmentlengthpolymorphism ,RFLP)分析。 结果 :胃癌组织、癌旁黏膜及正常胃黏膜中DCC基因 2 0 1密码子点突变率分别为 5 9.3%、5 3.7%和 10 %,胃癌组织与癌旁黏膜两者的突变率都明显高于正常胃黏膜 (P <0 .0 5 ) ,胃癌组织中以纯合突变为主 ,而癌旁黏膜中以杂合突变为主(P <0 .0 5 )。此外 ,2 0 1密码子的突变与胃癌的浸润深度、淋巴结转移和TNM分期存在正相关。结论 :DCC基因2 0 1密码子突变是胃癌发生的一个早期基因事件 ,并且该突变参与胃癌的进展和转移。临床上可以根据这一特点 ,对胃镜活检标本进行DCC基因 2 0 1密码子突变的分析 ,以筛选出可能发生胃癌的高危人群。

Objective: To detect the mutation of the deleted in colorectal cancer (DCC) gene codon 201 in gastric cancer and its correlation with clinicopathological parameters. Methods: Specimens of the gastric cancer tissue and the paracancer mucosa as well as the normal gastric mucosa were obtained from 54 operated patients with gastric cancer and 30 non-cancer patients respectively. Polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) was carried out to detect the mutation of DCC gene codon 201. Results: The frequency of the mutation of DCC gene codon 201 was 59.3%, 53.7% and 10% in the gastric cancer tissue, paracancer mucosa and normal mucosa, respectively. There was a higher mutation rate in the gastric cancer tissue and the paracancer mucosa than in the normal mucosa (P<0.05). The gastric cancer tissue demonstrated a dominance of homozygous mutation, while the paracancer mucosa a dominance of heterozygous mutation (P<0.05). Furthermore, there was a significantly positive correlation between the codon 201 mutation and the depth of tumor infiltration, lymph node involvement and TNM stage of gastric cancer. Conclusions: The mutation of DCC gene codon 201 is an early genetic event in the carcinogenesis of gastric cancer, and plays a role in tumor invasion and metastasis, which suggests that the codon 201 mutation might be served as a useful marker for screening high risk population by being detected in the bioptic specimens of gastroscopy.