J Lung Cancer.  2008 Dec;7(2):65-70. 10.6058/jlc.2008.7.2.65.

Detection of Serum Free DNA Hypermethylation in Surgically Resected Adenocarcinoma of the Lung

• Park SJ
• Kim YT
• Park JY
• Wi HC
• Kang CH
• Sung SW
• Kim JH

• KMID: 2200028
• DOI: http://doi.org/10.6058/jlc.2008.7.2.65

Abstract

PURPOSE : Aberrant DNA methylation patterns have been commonly associated with human cancers. We have investigated the frequency of DNA hypermethylation in promoter regions from adenocarcinomas of the lung and then attempted to detect the same epigenetic changes from patient serum samples.
MATERIALS AND METHODS
: We collected tissues from 72 cases of lung adenocarcinomas. The cancer and normal lung tissues were tested for DNA hypermethylation using methylation-specific PCR (MSP). The genes investigated were DAPK, RARbetaP2 and p16. We selected 12 patients where promoter hypermethylation was present for all three genes and four patients where hypermethylation was not seen for any of the three genes. Serum-free DNA was extracted and was tested for promoter hypermethylation. The status of serum-free DNA methylation was analyzed; the hypermethylation status was compared to clinical variables and cancer outcomes.
RESULTS
: DNA hypermethylation was observed in 32% of samples for DAPK, 63% of samples for RARbetaP2 and 83% of samples for p16 from the cancer tissues. Among the 12 matched serum samples where the primary tumor showed hypermethylation in all three gene promoter regions, we were able to detect five incidences of serum DNA hypermethylation in four patients. The four patients had TNM stage II or higher disease. None of the patients with stage I disease showed serum-free DNA hypermethylation.
CONCLUSION
: Aberrant promoter hypermethylation was frequently observed in surgically resected adenocarcinoma of the lung. Concurrent serum-free DNA hypermethylation was detected in 34% of patients where the primary tumor showed hypermethylation in all three gene promoter regions. The findings suggest that the serum-free DNA methylation status might be used as a potential target for the diagnosis of lung cancer. However, the low sensitivity should be improved for use in a clinical application

Keyword

Lung cancer; Adenocarcinoma; Hypermethylation; Epigenetics; Serum DNA

MeSH Terms

Adenocarcinoma
DNA
DNA Methylation
Epigenomics
Humans
Incidence
Lung
Lung Neoplasms
Polymerase Chain Reaction
Promoter Regions, Genetic
DNA

Figure

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  Fig. 1. Result of MSP analyses of serum-free DNA for three genes: DAPK, RARβ P2 and p16.

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  Fig. 2. Summary of the methylation status for DAPK, RARβ P2 and p16 in primary tumor and serum samples. The black-colored boxes represent methylated samples.

Reference

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