INACTIVATION OF THE CDKN2/pl6 GENE INDUCED BY METHYLATION AT 5'-CpG ISLAND AND ITS RELATION TO LUNG CANCER

摘要

Objectives: To investigate the methylation status of the CDKN2/pl6 gene 5’-CpG island, and study the relationship between the CDKN2/pl6 gene inacti-vation by methylation and lung cancer. Methods: Genomic DNA extracted from the specimens of lung cancer and normal lung tissue was digested with methylation-sensitive endonucleases, and Southern blotting was used to analyze the methylation status of the CDKN2/pl6 gene in 89 cases of lung cancer and 10 cases of normal lung tissue. Results: In 89 cases of lung cancer studied, the CDKN2/pl6 gene was shown to be methylated in 21 cases with the total methylation rate of 23.6% (21/89), in which there were 15 cases (16.9%) methylated at SmaI sites, 12 cases (13.5%) at SacII sites and 6 cases at both SmaI and SacII sites. The methylation of the CDKN2/pl6 gene occurred in 17 among 42 of pl6 protein negative cases of lung cancer with a rate of 40.5% (17/42), and in 3 among 47 of pl6 protein positive cases with a rate of 6.4% (3/47). The CDKN2/pl6 gene was not methylated in 10 cases of normal lung tissue. Conclusion: The aberrant methylation of the CDKN2/pl6 gene 5’-CpG island is probably an important mechanism of the gene inactivation, it may be involved in the genesis and progress of lung cancer.