Promoter Methylation Primarily Occurs in Tumor Cells of Patients with Non-small Cell Lung Cancer

Background: The distribution of promoter methylation throughout the lungs of patients with non-small cell lung cancer (NSCLC) is unknown. In this explorative study, we assessed the methylation status of the promoter region of 11 genes in brush samples of 3 well-defined endobronchial locations in patients with NSCLC and in brushes of former and current smokers without NSCLC. Materials and Methods: The methylation status of RASSF1A, GATA4, GATA5, SFRP1, RAR beta 2, DAPK, MGMT, p16, p14, CHFR and APC2 was determined in all samples using real-time methylation-specific PCR. Results: Ten patients with NSCLC and 18 non-NSCLC controls were included. Eight patients had one or more methylated genes in their tumor brush. Promoter methylation of genes in proximal or contralateral locations was much less frequent than in tumor brushes, and almost exclusively occurred in normal tissue if the same gene was also methylated in the tumor brush. Conclusion: Promoter methylation almost exclusively occurred in tumor cells of patients with NSCLC.