Original ContributionsAltered global methylation of DNA: An epigenetic difference in susceptibility for lung cancer is associated with its progression*,**
Section snippets
Patients and tissue specimens
Formalin-fixed, paraffin-embedded sections of the lung were obtained from the archival collections of the Veterans Administration Hospital and University Hospital in Birmingham, AL. Thirty noncancer specimens of the lung were selected at random from a list of lung surgeries performed in smokers between 1988 and 1998 for advanced emphysema of the lung. From a list of patients with SCC of the lung who had undergone surgery between 1989 and 1996, 60 cases were selected at random. Exposure to
Results
The 5-mc scores were reproducible for individual cases as well as for a group of tissue specimens. The average coefficient of variation of the assay was 4%. The mean ±SD for 5-mc scores of the 10 tissue sections stained and evaluated on 2 different days was 1.17 ± 0.3 and 1.16 ± 0.2. The specimens of all 30 noncancer subjects had adequate normal bronchial epithelium for the evaluation of immunostaining for 5-mc. Ten noncancer specimens also had hyperplastic lesions for evaluation. Metaplastic
Discussion
The observation that only a fraction of cigarette smokers develop lung cancer during their lifetimes is intriguing. Although the genetic and epigenetic differences between smokers who develop SCC and those who do not have substantial preventive implications, this field is still in its infancy. The present study focused on global methylation of DNA, an epigenetic change in DNA that may play a central role in the multistage process of human carcinogenesis. To our knowledge, this is the first
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2011, Biochemical and Biophysical Research CommunicationsCitation Excerpt :On days 15, 35, 55, 65, and 75 after instillation, animals were executed by exsanguination under anesthesia. Upon sacrifice, the left lungs were cut into two pieces, one of which was kept frozen, and the other was fixed by immersion in 4% formaldehyde in phosphate buffer for 24 h, embedded in paraffin, sectioned to 4 and 10 μm thickness, and routinely processed for histological examination [17]. Laser capture microdissection was performed using the Leica Laser LMD microdissector (Leica, Wetzlar, Germany) according to the manufacturer’s instructions.
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2011, Cancer LettersCitation Excerpt :In lung cancer, extensive DNA hypomethylation occurs specifically within nuclear elements, LTR elements, segmental duplications, and subtelomeric regions; whereas non-repetitive sequences are rarely demethylated [33]. Piyathilake and colleagues observed significant global DNA hypomethylation in squamous cell carcinoma of the lung, and indicated that the progression may be age-related [97,98]. Our group investigated DNA methylation patterns in TETs and found significant reductions in 5-methylcytosine content in TET cell DNA, especially in highly malignant tumors.
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Supported by grant K07 CA 70160 from the National Cancer Institute.
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Address correspondence and reprint requests to Chandrika J. Piyathilake, PhD, Department of Nutrition Sciences, Division of Nutritional Biochemistry and Molecular Biology, University of Alabama at Birmingham, University Station, Birmingham, AL 35294.