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DNA Methylation in Tumor and Matched Normal Tissues from Non-Small Cell Lung Cancer Patients

Departments of ¹ Pathology and ² Radiology, School of Medicine and Department of ³ Epidemiology, School of Public Health and Community Medicine, University of Washington and ⁴ Veterans Affairs Puget Sound Health Care System, Seattle, Washington

Requests for reprints: Hubert Vesselle, Department of Radiology, School of Medicine, University of Washington, Box 357115, Seattle, WA 98195-7115. Phone: 206-221-4309; Fax: 206-543-6317. E-mail: vesselle{at}u.washington.edu

We used MethyLight assays to analyze DNA methylation status of 27 genes on 49 paired cancerous and noncancerous tissue samples from non-small cell lung cancer (NSCLC) patients who underwent surgical resection. Seven genes (RARB, BVES, CDKN2A, KCNH5, RASSF1, CDH13, and RUNX) were found to be methylated significantly more frequently in tumor tissues than in noncancerous tissues. Only methylation of CCND2 and APC was frequently detected in both cancerous and noncancerous tissues, supporting the hypothesis that the methylation of these two genes is a preneoplastic change and may be associated with tobacco smoking exposure. Methylation of any one of eight genes (RASSF1, DAPK1, BVES, CDH13, MGMT, KCNH5, RARB, or CDH1) was present in 80% of NSCLC tissues but only in 14% of noncancerous tissues. Detection of methylation of these genes in blood might have utility in monitoring and detecting tumor recurrence in early-stage NSCLC after curative surgical resection. (Cancer Epidemiol Biomarkers Prev 2008;17(3):645–54)