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用PCR-SSCP分析法对36例矽肺患者的石蜡包埋的原发性肺癌组织p53基因第5、7、8外显子进行了检测,检出突变15例。突变在第5、7、8外显子上都有发生,但以第8外显子上发现的阳性突变最多。对肿瘤类型和p53基因突变的关系进行了分析,发现矽肺病例肺腺癌p53基因阳性突变率最高,为53.9%,高于普通型肺癌(33.0%)。进一步对其中1例样本进行核苷酸序列直接测定,结果显示第5外显子非突变热点区的第144位密码子核苷酸由CAG突变为AAG,氨基酸由谷氨酰胺突变为赖氨酸,以上结果与非职业肺癌明显不同,提示p53基因突变在矽肺病例肺癌发生中起着重要作用,可能与矽尘作业环境中含有的某些化学致癌物有关。
PCR-SSCP analysis was used to detect the exon 5, 7 and 8 of p53 gene in paraffin-embedded primary lung cancer tissues of 36 patients with silicosis. 15 mutations were detected. Mutations occurred on exons 5, 7, and 8, but the most positive mutations were found on exon 8. The relationship between tumor type and p53 gene mutation was analyzed. It was found that the rate of p53 gene positive mutation in lung adenocarcinoma was the highest, 53.9%, higher than that of normal lung cancer (33.0%). A direct measurement of the nucleotide sequence of one sample was performed. The results showed that the 144th codon nucleotide in the non-mutation hot spot of exon 5 was mutated from CAG to AAG and the amino acid was mutated to lysine from glutamine. The above results are obviously different from those of non-professional lung cancer, suggesting that p53 gene mutation plays an important role in the occurrence of lung cancer in silicosis cases, and may be related to certain chemical carcinogens contained in the whisking environment.