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Lung Carcinogenesis Tracked By DNA Methylation Mapping In Exhaled Breath

Date:
November 13, 2006
Source:
American Association For Cancer Research
Summary:
For the first time, researchers have demonstrated that it is possible to detect DNA methylation in the breath of smokers and lung cancer patients, suggesting that, in theory, it may be possible to use this technique to identify people who have undiagnosed lung cancer or are at high risk of developing the disease.
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For the first time, researchers have demonstrated that it is possible to detect DNA methylation in the breath of smokers and lung cancer patients, suggesting that, in theory, it may be possible to use this technique to identify people who have undiagnosed lung cancer or are at high risk of developing the disease.

Investigators at the Wadsworth Center, the public health laboratory of the New York State Department of Health, have been able to develop an assay that simultaneously detects the presence of methylation in six tumor suppressor genes - a process by which a gene is chemically silenced. The assay examines the promoter region of a gene, where certain cytosine nucleotide bases may be methylated, preventing the gene from being expressed.

The seven participants tested so far breathe for ten minutes into a commercially available handheld device, which cools the air, forming a condensed vapor, to which the methylation assay is applied. Investigators found it could detect the presence of the methylated form in all six tumor suppressor genes. For RASSF1A, the test was negative in non-smokers, and positive in both current and ex-smokers. For DAPK, methylation was more variable, given smoking status. The four other tested genes (p16, MGMT, PAX5B,CDH1) known to be methylated in various stages of lung cancer development, were minimally or not methylated, in this pilot study of predominantly cancer-free smokers.

"Dr. Weiguo Han and I have shown that this approach is technically feasible, and if further research demonstrates the assay can measure DNA in such a way that it diagnoses or predicts lung cancer, this could be important for non-invasive lung cancer testing," said the study's lead author, Simon D. Spivack, M.D., M.P.H., a research physician at the Wadsworth Center, and a specialist in lung diseases. "But we are a long way from that point." Han, a post-doctoral fellow in Spivacks' laboratory and the study's first author, will be presenting the findings.

Spivack said his study was only the third to date that proved DNA could be tested in condensed breath - German researchers reported the first such result in 2003, followed by an Italian group in 2005 - and the first to find methylation-silenced tumor suppressor genes in the breath of patients at risk or harboring lung cancer.

"The concept of testing exhaled breath is not new - that's what breathalyzers do when they measure small volatile molecules such as alcohol, as well as inflammation molecules that are currently being assayed to test the activity of asthma and other lung diseases," said Spivack. "But what is rather remarkable here is that DNA can be tested in the air that comes from the lungs and airways, and that it might be possible to use this in diagnosis of lung cancer in particular, and gene-dysregulation disorders of the lung, in general."

The DNA is believed to be released when cells turn over, or are damaged, in the lungs and airways, he said. "Although it is not possible to say at this point the precise anatomic origin of the airway-derived DNA being tested, it may be that different patterns of gene methylation will themselves actually map the origin of this DNA to particular regions of the airway," Spivack said.

"Our goal is early detection of lung cancer and risk stratification," he said. "If all we can do is confirm that a smoker is smoking, or that a lung cancer patient has cancer, then this test will be meaningless. But we now know it is technically feasible to measure DNA methylation in breath."


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The above story is based on materials provided by American Association For Cancer Research. Note: Materials may be edited for content and length.


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American Association For Cancer Research. "Lung Carcinogenesis Tracked By DNA Methylation Mapping In Exhaled Breath." ScienceDaily. ScienceDaily, 13 November 2006. <www.sciencedaily.com/releases/2006/11/061112235348.htm>.
American Association For Cancer Research. (2006, November 13). Lung Carcinogenesis Tracked By DNA Methylation Mapping In Exhaled Breath. ScienceDaily. Retrieved May 24, 2015 from www.sciencedaily.com/releases/2006/11/061112235348.htm
American Association For Cancer Research. "Lung Carcinogenesis Tracked By DNA Methylation Mapping In Exhaled Breath." ScienceDaily. www.sciencedaily.com/releases/2006/11/061112235348.htm (accessed May 24, 2015).

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