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Genome-wide analysis of DNA methylation and the gene expression change in lung cancer

Authors :
Jong Ho Park
Yong Jae Kwon
Jae Bum Bae
Moon Chul Kang
Young Joon Kim
Jae Soo Koh
Sung Han Kim
Hae Won Lee
Seog Joo Lee
Source :
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer. 7(1)
Publication Year :
2011

Abstract

Introduction The recent DNA methylation studies on cancers have revealed the necessity of profiling an entire human genome and not to restrict the profiling to specific regions of the human genome. It has been suggested that genome-wide DNA methylation analysis enables us to identify the genes that are regulated by DNA methylation in carcinogenesis. Methods So, we performed whole-genome DNA methylation analysis for human lung squamous cell carcinoma (SCC), which is strongly related with smoking. We also performed microarrays using 21 pairs of normal lung tissues and tumors from patients with SCC. By combining these data, 30 hypermethylated and down-regulated genes, and 22 hypomethylated and up-regulated genes were selected. The gene expression level and DNA methylation pattern were confirmed by semiquantitative reverse-transcriptase polymerase chain reaction and pyrosequencing, respectively. Results By these validations, we selected five hypermethylated and down-regulated genes and one hypomethylated and up-regulated gene. Moreover, these six genes were proven to be actually regulated by DNA methylation by confirming the recovery of their DNA methylation pattern and gene expression level using a demethylating agent. The DNA methylation pattern of the CYTL1 promoter region was significantly different between early and advanced stages of SCC. Conclusion In conclusion, by combining the whole-genome DNA methylation pattern and the gene expression profile, we identified the six genes ( CCDC37 , CYTL1 , CDO1 , SLIT2 , LMO3 , and SERPINB5 ) that are regulated by DNA methylation, and we suggest their value as target molecules for further study of SCC.

Details

ISSN :
15561380
Volume :
7
Issue :
1
Database :
OpenAIRE
Journal :
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
Accession number :
edsair.doi.dedup.....be216d2f30c23bdf1863ed5a95ccd8e2