title: Aberrant DNA methylation profile in pleural fluid for differential diagnosis of malignant pleural mesothelioma.
abstract: Malignant pleural mesothelioma (MPM) usually develops pleural fluid. We investigated the value of DNA methylation in the pleural fluid for differentiating MPM from lung cancer (LC). Pleural fluid was collected from 39 patients with MPM, 46 with LC, 25 with benign asbestos pleurisy (BAP) and 30 with other causes. The methylation of O(6)-methylguanine-DNA methyltransferase (MGMT), p16(INK4a) , ras association domain family 1A (RASSF1A), death-associated protein kinase (DAPK), and retinoic acid receptor β (RARβ) was examined using quantitative real-time PCR. DNA methylation of RASSF1A, p16(INK4a), RARβ, MGMT and DAPK was detected in 12 (30.8%), 3 (7.7%), 11 (28.2%), 0 (0.0%) and five patients (12.8%) with MPM, and in 22 (47.8%), 14 (30.4%), 24 (52.2%), 1 (2.2%) and six patients (13.0%) with LC, respectively. The mean methylation ratios of RASSF1A, p16(INK4a) and RARβ were 0.37 (range 0.0-2.84), 0.11 (0.0-2.67) and 0.44 (0.0-3.32) in MPM, and 0.87 (0.0-3.14), 1.16 (0.0-5.35) and 1.69 (0.0-6.49) in LC, respectively. The methylation ratios for the three genes were significantly higher in LC than in MPM (RASSF1A, P = 0.039; p16(INK4a), P = 0.005; and RARβ, P = 0.002). Patients with methylation in at least one gene were 3.51 (95% confidence interval, 1.09-11.34) times more likely to have LC. Hypermethylation seemed no greater with MPM than with BAP. Extended exposure to asbestos (≧30 years) was correlated with an increased methylation frequency (P = 0.020). Hypermethylation of tumor suppressor genes in pleural fluid DNA has the potential to be a valuable marker for differentiating MPM from LC.
authors.affiliation: Department of Respiratory Medicine, Okayama Rosai Hospital, Okayama, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Fujii
authors.forename: Nobukazu
authors.initials: N
authors.lastname: Fujimoto
authors.forename: Akio
authors.initials: A
authors.lastname: Hiraki
authors.forename: Kenichi
authors.initials: K
authors.lastname: Gemba
authors.forename: Keisuke
authors.initials: K
authors.lastname: Aoe
authors.forename: Shigeki
authors.initials: S
authors.lastname: Umemura
authors.forename: Hideki
authors.initials: H
authors.lastname: Katayama
authors.forename: Nagio
authors.initials: N
authors.lastname: Takigawa
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Kiura
authors.forename: Mitsune
authors.initials: M
authors.lastname: Tanimoto
authors.forename: Takumi
authors.initials: T
authors.lastname: Kishimoto
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001194:Asbestos / Q000009:adverse effects; D001826:Body Fluids; D019175:DNA Methylation / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D003937:Diagnosis, Differential; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D008654:Mesothelioma / Q000139:chemically induced / Q000175:diagnosis* / Q000235:genetics; D008875:Middle Aged; D010997:Pleural Neoplasms / Q000139:chemically induced / Q000175:diagnosis* / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D004273:DNA, Neoplasm; D001194:Asbestos