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目的 探讨FHIT等位基因缺失、突变在肺癌发生、发展中的作用。方法 应用PCR SSCP和DNA序列分析方法对 3 5例人非小细胞肺癌和 4个肺癌细胞株中FHIT基因的 4个外显子 (外显子 3、4、5、8)和微卫星D3S13 0 0、D3S13 12、D3S13 13进行研究 ,并以远癌肺组织和 10例肺良性病变组织做对照。结果 在 3 5例肺癌中 ,2 2例肺癌发生了一个或两个以上的FHIT等位基因缺失 ,缺失率为 62 .86% ( 2 2 /3 5 )。在鳞癌中 ,FHIT等位基因缺失率 ( 88.2 4% ,15 /17)明显高于腺癌 ( 3 8.89% ,7/18) (P <0 .0 1) ;在吸烟患者中 ( 76.19% ,16/2 1)亦明显高于不吸烟患者 ( 4 2 .86% ,6/14 ) (P <0 .0 5 )。而FHIT等位基因缺失与肺癌的细胞分化程度、P TNM分期、原发肿瘤大小、部位、患者性别、年龄及有无转移均无明显关系 (P >0 .0 5 )。Lewis肺癌、A5 49细胞株亦有FHIT基因部分缺失。 4例肺癌组织具有微卫星灶D3S13 12点突变 ,经DNA序列分析显示均为D3S13 12微卫星灶基因的 87位点密码子发生了CT点突变。结论 FHIT基因异常主要以等位基因的缺失为主 ,而点突变发生率较低。FHIT等位基因缺失主要发生在肺鳞癌和吸烟患者中 ,且FHIT基因可能为烟草致肺癌的靶基因 ,其等位基因缺失可能是肺癌的早期分子事件。
Objective To investigate the role of deletion and mutation of FHIT alleles in the development and progression of lung cancer. Methods The four exons (exons 3, 4, 5, 8) and microsatellite D3S13 of the FHIT gene in 35 human non-small cell lung cancer and 4 lung cancer cell lines were analyzed by PCR-SSCP and DNA sequencing. 0, D3S13 12, D3S13 13 were studied, and compared with distant lung cancer tissues and 10 benign pulmonary lesions. Results Of the 35 lung cancer cases, one or two FHIT alleles were missing in 22 cases of lung cancer. The deletion rate was 62.86% (22/35). In squamous cell carcinoma, the FHIT allele deletion rate (88.2 4%, 15/17) was significantly higher than that of adenocarcinoma (3 8.89%, 7/18) (P <0. 01); in smoking patients (76.19%) , 16/2 1) was also significantly higher than non-smoking patients (42.86%, 6/14) (P < 0.05). The loss of FHIT allele was not significantly associated with the degree of lung cancer cell differentiation, P TNM stage, primary tumor size, location, patient gender, age, and metastasis (P > 0.05). Lewis lung cancer and A5 49 cell lines also have partial deletion of the FHIT gene. In 4 cases of lung cancer, there was a 12-point mutation in D3S13 of microsatellite loci. DNA sequence analysis revealed that C-T mutations occurred at the 87-site codon of the D3S13 12-satellite gene. Conclusion The major allele of FHIT gene is loss of alleles, but the incidence of point mutations is low. FHIT allele deletion mainly occurs in lung squamous cell carcinoma and smoking patients, and the FHIT gene may be a target gene for tobacco-induced lung cancer. The allele deletion may be an early molecular event of lung cancer.