Tuberc Respir Dis.  2000 Oct;49(4):453-465. 10.4046/trd.2000.49.4.453.

Genetic alteration of tumor suppressor gene and microsatellite in nonsmall cell lung cancer

Abstract

BACKGROUND
Lung carcinogenesis is a multistage process involving alterations in multiple genes and diverse pathway. Mutational activation of oncogenes and inactivation of tumor suppressor genes, and subsequent increased genetic instability are the major genetic events. The p53 gene and FHIT gene as tumor suppressor genes contribute to the pathogenesis of lung cancer, evidenced by mutation, microsatellite instability(MI) and loss of heterozygosity(LOH).
METHODS
We analysed genetic mutations of p53 and FHIT gene in 29 surgical specimens of nonsmall cell lung cancer using PCR-single strand conformation polymorphism, DNA sequencing and RT-PCR. MI and LOH were analyzed in loci of D3S1285, D9S171, and TP53.
RESULTS
In 2 cases, point mutation of p53 gene was observed on exon 5. MI of 3 times and LOH of 14 times were observed in at least one locus. In terms of the location on microsatellite, D3S1285 as a marker of FHIT was observed in 5 cases out of 26 specimens;D9S171 as a marker of p16 in 5 out of 17;and TP53 as a marker of p53 in 7 out of 27. In view of histologic type, squamous cell carcinoma presented higher frequency of microsatellite alteration, compared to others. Mutation of FHIT gene was observed in 11 cases and 6 cases of those were point mutation as a silent substitution on exon 8. FHIT mRNA expression exhibited deletion on exon 6 to 9 in 4 cases among 15 specimens, presenting beta-actin normally.
CONCLUSION
Our results show comparable frequency of genetic alteration in nonsmall cell lung cancer to previous studies of Western countries. Microsatellite analysis might have a role as a tumor marker especially in squamous cell carcinoma. Understanding molecular abnormalities involved in the pathogenesis could potentially lead to prevention, earlier diagnosis and the development of novel investigational approaches to the treatment of lung cancer.

Keyword

P53; FHIT; Nonsmall cell lung cancer; Microsatellite instability; Loss of heterozygosity

MeSH Terms

Actins
Carcinogenesis
Carcinoma, Non-Small-Cell Lung*
Carcinoma, Squamous Cell
Diagnosis
Exons
Genes, p53
Genes, Tumor Suppressor*
Loss of Heterozygosity
Lung
Lung Neoplasms
Microsatellite Instability
Microsatellite Repeats*
Oncogenes
Point Mutation
RNA, Messenger
Sequence Analysis, DNA
Actins
RNA, Messenger
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