title: Deoxyribonucleic acid (DNA) methyltransferase contributes to p16 promoter CpG island methylation in lung adenocarcinoma with smoking.
abstract: In this study, the relationship between CpG island methylation and smoking and DNA methyltransferase in the occurrence and development of lung adenocarcinoma was explored by detecting p16 promoter methylation status. Protein and mRNA levels of p16 were detected by immunohistochemistry and in situ hybridization assays. p16 gene promoter and exon 1 CpG island locus Hap II sites methylation status was analyzed with the methylation-specific PCR. Only 4 of 40 p16-positive cases were detected to methylate on CpG islands with 10% methylating rate whereas 18 of p16-negative cases were methylated up to 36.73% of methylating rate. The methylating rates of both p16-positive and p16-negative groups were significantly different. 17 of 50 cases with smoking from total 89 lung adenocarcinoma cases were detected to methylate on CpG islands while only 5 of the remaining 39 non-smokers to methylate. The difference of the methylating rates in both smokers and non-smokers was significant to suggest the closely association of CpG island methylation of p16 with smoking. Furthermore, p16 promoter CpG islands were detected to methylate in 15 of 35 cases with higher DNA methyltransferase activity whereas only 7 detected to methylate in the remaining 54 cases with lower DNA methyltransferase activity. p16 promoter CpG island methylation likely made p16 expressing silence thus contributed to the tumorigenesis of lung adenocarcinoma. Smoking is likely to promote p16 CpG island methylation or by its effect of the activity and metabolism of DNA methyltransferase 1 (DNMT) on CpG island methylation status.
authors.affiliation: Department of Emergency, General Hospital of PLA Beijing 100853, China.
authors.forename: Rongju
authors.initials: R
authors.lastname: Sun
authors.affiliation: The Second Affiliated Hospital of Qingdao University Medical College, Qingdao Central Hospital, Institute of Tuberculosis and Pulmonary Qingdao 266042, China.
authors.forename: Jiahong
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Thoracic Surgery, General Hospital of PLA Beijing 100853, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Respiration, The First Affiliated Hospital of General Hospital of PLA Beijing 100048, China.
authors.forename: Lingyun
authors.initials: L
authors.lastname: Ma
authors.affiliation: Department of Emergency, Affiliated Hainan Hospital, General Hospital of PLA Sanya 572000, China.
authors.forename: Xiaojiao
authors.initials: X
authors.lastname: Quan
authors.affiliation: Department of Emergency, Affiliated Hainan Hospital, General Hospital of PLA Sanya 572000, China.
authors.forename: Zhixiang
authors.initials: Z
authors.lastname: Chu
authors.affiliation: Department of Emergency, General Hospital of PLA Beijing 100853, China.
authors.forename: Tanshi
authors.initials: T
authors.lastname: Li
keywords: DNA methyltransferase; lung adenocarcinoma; methylation; p16 tumor suppressor gene; smoking