Zhou Q, Chen J, Qin Y, Sun Z, Liu L, Sun Z, Che G, Li L, Qin J, Gong Y
Department of Thoracocardiac Surgery, The First University Hospital, West China University of Medical Sciences, Chengdu, Sichuan 610041, P.R.China.
Zhongguo Fei Ai Za Zhi. 2001 Feb 20;4(1):10-4. doi: 10.3779/j.issn.1009-3419.2001.01.04.
To explore the role of the allelic deletion and mutation of FHIT gene on the carcinogenesis and development of lung cancer.
The allelic alterations of FHIT gene and microsatellites D3S1300, D3S1312,D3S1313 were detected in 35 cancer samples of NSCLC, their corresponding normal tissues, and 4 lung cancer cell lines, and 10 lung tissues of benign pulmonary lesions as control by PCR-SSCP and DNA sequence.
Loss of heterozygosity (LOH) affecting at least one locus of FHIT gene was observed in 22 out of 35 tumors, with a LOH rate of 62.86%. LOH of FHIT gene in squamous cell carcinoma (88.24%) was significantly higher than that in adenocarcinoma (38.89%) (P<0.01). The LOH rate of FHIT gene in smoking patients (76.19%) was also significantly higher than that in non-smoking patients (42.86%)(P<0.05).No significant relationship was found among the LOH of FHIT and cell differentiation, P-TNM stages, size of primary tumor, location of cancer and age of the patients (P>0.05). LOH of FHIT was also detected in Lewis lung cancer and A549 cell lines. Mutation of microsatellite D3S1312 was observed in 4 lung cancer tissues. DNA sequence showed that C->T mutation occurred in the 87 codon of microsatellite D3S1312.
The alteration of FHIT gene is mainly allelic loss and the frequency of allelic mutation is rare. FHIT gene alterations preferentially occur in squamous cell carcinoma patients and smokers, and FHIT gene may be a candidate molecular target of carcinogenesis in tobacco smoker. Allelic deletion of FHIT gene might be an early molecular event in smoking-related lung cancer.
探讨FHIT基因的等位基因缺失和突变在肺癌发生发展中的作用。
采用PCR-SSCP及DNA测序技术，检测35例非小细胞肺癌癌组织及其相应正常组织、4种肺癌细胞系，以及作为对照的10例良性肺病变组织中FHIT基因和微卫星D3S1300、D3S1312、D3S1313的等位基因改变。
35例肿瘤组织中，22例（62.86%）至少有一个位点出现FHIT基因杂合性缺失（LOH）。肺鳞癌中FHIT基因LOH率（88.24%）显著高于肺腺癌（38.89%）（P<0.01）。吸烟患者FHIT基因LOH率（76.19%）也显著高于非吸烟患者（42.86%）（P<0.05）。FHIT基因LOH与细胞分化程度、P-TNM分期、原发肿瘤大小、肿瘤部位及患者年龄之间无显著相关性（P>0.05）。在Lewis肺癌细胞系和A549细胞系中也检测到FHIT基因LOH。4例肺癌组织中观察到微卫星D3S1312突变。DNA序列分析显示，微卫星D3S1312第87密码子发生C→T突变。
FHIT基因改变主要为等位基因缺失，等位基因突变频率较低。FHIT基因改变在肺鳞癌患者和吸烟者中更易发生，FHIT基因可能是吸烟相关肺癌发生的候选分子靶点。FHIT基因的等位基因缺失可能是吸烟相关肺癌的早期分子事件。
