Distinct DNA methylation profiles in malignant mesothelioma, lung adenocarcinoma, and non-tumor lung

DNA methylation markers provide a powerful toot to make diagnoses based on genetic material obtained directly from tumors or from "remote" locations such as sputum, pleural fluid, or serum. In particular when limited cell numbers are available, amplifyabte DNA markers can provide a very sensitive toot for cancer detection and classification. Malignant mesothelioma (MM), an aggressive cancer strongly associated with asbestos exposure, can be difficult to distinguish from adenocarcinoma of the lung when limited material is available. In an attempt to identify molecular markers for MM and adenocarcinoma, we examined the DNA methylation status of 14 loci. Analysis of methylation levels in 10 MM and 8 adenocarcinoma cell lines showed that methylation of APC was significantly elevated in adenocarcinoma compared to MM cell tines (P=0.0003), white methylation of CDH1 was higher in MM (P < 0.02). Subsequent examination of the methylation status of the 14 loci in 6 MM and 7 adenocarcinoma primary tumors, which yielded similar methylation profiles, supported these observations. Comparison of methylation in MM cell lines and tu mors versus non-tumor lung tissue indicated that APC exhibits less methylation in MM (P=0.003) white RASSR, PGR1, ESR1, and CDH1 show more methylation in MM, the latter two showing the most significant difference between the two tissue types I (P <= 0.0001). Comparison of methylation in adenocarcinoma cell tines and tumors very, sus non-tumor lung tissue showed methylation of ESR1, PGR1 and RASSF1 to be significantly elevated in adenocarcinoma, with RASSR being most significant. (P= 0.0002). Thus, with the examination of 14 loci, we have identified 5 candidates that show potential for distinguishing between MM, adenocarcinoma and/or non-cancer lung. Our observations support the strong potential of methylation markers as toots for accurate diagnosis of neoplasms in and around the lung. (C) 2004 Elsevier Ireland Ltd. All rights reserved.