Epigenome-Wide Dna Methylation Profiling Of Lung Tumors From Asbestos-Exposed Patients

Introduction and objectives. Epigenetic modifications such as changes in DNA methylation have been shown as response to many toxic exposures. However, not much is known about the role of epigenetics in human lung carcinogenesis associated with asbestos exposure. Here, we explored the epigenome-wide DNA methylation (DNA methylome) patterns in lung tumors focused on asbestos-exposed and non-exposed patients who were mostly smokers. We sought to investigate whether methylation markers in lung cancer associate with exposure (asbestos, tobacco smoke) and clinico-pathological features. Study design, subjects, and methods. The DNA methylome was examined by Illumina Infinium 450K HumanMethylation technology covering more than 450 000 CpG sites. Validation experiments were done by pyrosequencing. DNA methylation was studied in lung tumors and normal lung as matched pairs obtained from 28 patients from lung surgery in Helsinki during years 1988-1996. Detailed data on the patients’ work and smoking histories, pulmonary fiber counts (14 asbestos-exposed and 14 non-exposed), and clinical data were available. As controls, normal lung specimens from patients with non-malignant lung disease were studied for genome-wide DNA methylation. Results. DNA methylation profiles differed in relation to sample type, tumor histology and exposure status. We identified more than 10.000 methylation variable positions (MVPs) that differed (adjusted P Conclusions. Our analysis suggests that methylation profiles were globally affected in lung tumors in comparison to matched normal lung. We also found associations to asbestos exposure and tobacco smoking, suggesting a role for these exposures in modification of DNA methylome profiles. Citation Format: Eeva M. Kettunen, Hector Hernandez-Vargas, Marie-Pierre Cros, Geoffroy Durand, Florence Le Calvez-Kelm, Henrik Wolff, Kaisa Salmenkivi, Sisko L. Anttila, Zdenko Herceg, Kirsti Husgafvel-Pursiainen. Epigenome-wide DNA methylation profiling of lung tumors from asbestos-exposed patients. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1060. doi:10.1158/1538-7445.AM2015-1060