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

Yong Jae Kwon, Seog Joo Lee, Jae Soo Koh, Sung Han Kim, Hae Won Lee, Moon Chul Kang, Jae Bum Bae, Young Joon Kim, Jong Ho Park

Research output: Contribution to journalArticlepeer-review

65 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)20-33
Number of pages14
JournalJournal of Thoracic Oncology
Volume7
Issue number1
DOIs
Publication statusPublished - 2012 Jan

Bibliographical note

Funding Information:
Supported by National Research Foundation grant funded by the Korea government (MEST) (2010-0020534) and (2010020536). The management of clinical data used in this article was supported by Registration of Cancer Patients and Establishment of Clinical Database grant of Korea Cancer Center Hospital.

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pulmonary and Respiratory Medicine

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