| Summary: | 碩士 === 高雄醫學院 === 醫學研究所 === 86 === It has been proposed that the patterns of mutations in the p53
tumor suppressors gene will provide clues to the mechanisms of
cancer occurrence. Cigarette smoking is known to be the greatest
risk factor for lung cancer. Epidemiological evidence has also
implicated radon and asbestos as exposures that significantly
increase this disease risk ; asbestos exposure synergistically
enhances the lung cancer risk of smokers. Mutations of the p53
tumor suppressor gene, whose encoded protein is one of the chief
regulators of the cell cycle, are proving to be the most common
genetic alteration in human cancer. Point mutations have been
detected in numerous human solid tumors. The types of point
mutations in the p53 gene vary considerably in different kinds
and sites of mutations in the p53gene.Lung cancer is the leading
and second-leading cause of cancer deaths among women and men in
Taiwan, respectively. However, the molecular mechanisms involved
in lung tumorigenesis in Taiwan remain poorly defined.
Therefore, to gain insight into the role of the p53 tumor
suppressor gene and possible etiological factors in lung
tumorigenesis in Taiwan. We investigated the mutation spectra of
exons 4─8 in the p53 tumor suppressor gene of 27 lung cancer
patients in Taiwan. These data were also correlated with
clinical pathological characteristics of patients. Lung tumor
was surgically resected, genomic DNA was isolated, and their
mutation spectra were examined using PCR/SSCP (single-strand
conformational polymorphism) analysis 、direct sequencing and
auto sequencing. The frequency of p53 gene mutation was 14.8 %(4
of 27). Two of four mutations have the same mutation position,
codon 209(AGA→TGA), having alter the amino acid sequence from
Arg to Stop codon meaning nonsense mutation. The other two
mutations are the same mutation positions including codon
264(CTA(Leu)→ATA(Ile)) and codon 278(CCT(Pro)→CTT(Leu)). In
addition to codon 264 and codon 278 mutations, case 2 also has
codon 224(GAG →GAGG) insertion mutation, having alter the amino
sequence inducing frameshift mutation. Several kinds of
transversion and transition in our study are different from
previous study in mostly G→T transversion. In our studies , 3
of 4 mutations occurred in patients suffering from
adenocarcinoma is different from the Wang .et al study which has
the finding of high frequency of deletion mutation in p53 gene
from squamous cell lung cancer patients in Taiwan. In addition,
mutations were not correlated with patients'' smoking habits,
sex, age, occupational status, passivesmoking, cooking habits,
and incense burning. Our data suggest that we collectthe sample
size too small so we can not get the same data to other studies.
Key words: nonsense mutation, insertion mutation, frameshift
mutation, transvertion, transition
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