DNA Methylation in Lung Cancer.
- Author:
Min Ki LEE
1
Author Information
1. Department of Internal Medicine Pusan National University, Hospital, Korea. leemk98@dreamwiz.com
- Publication Type:Review
- Keywords:
DNA methylation;
Lung cancer
- MeSH:
Carcinogens;
Carcinoma, Non-Small-Cell Lung;
Cell Cycle;
CpG Islands;
Cyclin-Dependent Kinase 4;
Cyclin-Dependent Kinase Inhibitor p16;
Cytosine;
DNA Methylation*;
DNA*;
G1 Phase;
Genes, vif;
Genome;
Lung Neoplasms*;
Lung*;
Methylation;
Promoter Regions, Genetic;
Smoke;
Smoking;
Tobacco;
Vertebrates
- From:Journal of Lung Cancer
2002;1(1):23-28
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
DNA modification in vertebrate genomes is confined to the self-complementary sequence CpG. Between 60% and 90% of CpGs are methylated at the 5 position of cytosine, and the remainder is unmodified. Attempts to understand the function of CpG methylation have centered on its relationship to transcription. Introduction of methylated and nonmethylated genes into cells has shown that CpG methylation when applied near the promotor of a gene is often incompatible with efficient transcription. In addition, de novo methylation of sequences can occur naturally during development, and this has also been shown to interfere with transcription. Although there is no direct evidence that smoking induces DNA methylation, recent reports have associated DNA methylation with exposure to tobacco carcinogen. The p16INK4a protein inhibits cyclin-dependent kinase 4, a key regulator of progression through the G1 phase of the cell cycle. Methylation of CpG islands in the promotor region is an important avenue for inactivation of p16. The mechanism of methylation of the p16 promotor region, however, has not been elucidated. Recent reports investigating p16 methylation in non-small cell lung cancer (NSCLC) suggest that carcinogens in tobacco smoke induce the DNA methylation process. Methylation of CpG islands in tobacco-associated cancers occurs in a gene and tissue specific manner and is induced directly or indirectly by exposure to tobacco smoke in NSCLC.
