[A study on the allelic deletion and mutation of FHIT gene in human non-small cell lung cancer].
BACKGROUND
To explore the role of the allelic deletion and mutation of FHIT gene on the carcinogenesis and development of lung cancer.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Thoracocardiac Surgery, The First University Hospital, West China University of Medical Sciences, Chengdu, Sichuan 610041, P.R.China.
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Q
Zhou
J
J
Chen
Y
Y
Qin
Z
Z
Sun
L
L
Liu
Z
Z
Sun
G
G
Che
L
L
Li
J
J
Qin
Y
Y
Gong