Promoter Methylation of CDKN2A , RARβ , and RASSF1A in Non-Small Cell Lung Carcinoma: Quantitative Evaluation Using Pyrosequencing

Tuberculosis and Respiratory Diseases

article

Jung Uee Lee¹  Hae Joung Sul¹  Ji Woong Son² 

[1] Department of Pathology, St. Mary's Hospital, The Catholic University of Korea School of Medicine;Department of Internal Medicine, Konyang University Hospital, Konyang University College of Medicine

关键词: DNA Methylation;    Genes;    p16;    RASSF1 Protein;    Human;    Receptors;    Retinoic Acid;    Sequence Analysis;    DNA;    Carcinoma;    Non-Small Cell Lung;   

DOI  :  10.4046/trd.2012.73.1.11

学科分类：医学（综合）

来源: The Korean Academy of Tuberculosis and Respiratory Diseases

【 摘 要 】

Background While qualitative analysis of methylation has been reviewed, the quantitative analysis of methylation has rarely been studied. We evaluated the methylation status of CDKN2A , RARβ , and RASSF1A promoter regions in non-small cell lung carcinomas (NSCLCs) by using pyrosequencing. Then, we evaluated the association between methylation at the promoter regions of these tumor suppressor genes and the clinicopathological parameters of the NSCLCs. Methods We collected tumor tissues from a total of 53 patients with NSCLCs and analyzed the methylation level of the CDKN2A , RARβ , and RASSF1A promoter regions by using pyrosequencing. In addition, we investigated the correlation between the hypermethylation of CDKN2A and the loss of p16 INK4A immunoexpression. Results Hypermethylation of CDKN2A , RARβ , and RASSF1A promoter regions were 16 (30.2%), 22 (41.5%), and 21 tumors (39.6%), respectively. The incidence of hypermethylation at the CDKN2A promoter in the tumors was higher in undifferentiated large cell carcinomas than in other subtypes (p=0.002). Hyperrmethylation of CDKN2A was significantly associated with p16 INK4A immunoexpression loss (p=0.045). With regard to the clinicopathological characteristics of NSCLC, certain histopathological subtypes were found to be strongly associated with the loss of p16 INK4A immunoexpression (p=0.016). Squamous cell carcinoma and undifferentiated large cell carcinoma showed p16 INK4A immunoexpression loss more frequently. The Kaplan-Meier survival curves analysis showed that methylation level and patient survival were barely related to one another. Conclusion We quantitatively analyzed the promoter methylation status by using pyrosequencing. We showed a significant correlation between CDKN2A hypermethylation and p16 INK4A immunoexpression loss.

【 授权许可】

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