Abnormal promoter methylation of multiple tumor suppressor genes in human bronchial epithelial malignant cells.

Carcinoma of the lung is the leading cause of cancer-related mortality worldwide. In order to understand the pathogenesis of radiation-induced lung cancer, we adopted a model of transformed human bronchial epithelial cells (BEP2D) induced by α-particles. Methylation-specific polymerase chain reaction was performed to detect aberrant promoter methylation of multiple tumor suppressor genes, including p14ARF, p16INK4a, O6-methylguanine-DNA methyltransferase, glutathione S-transferase P1 and death-associated protein kinase genes in the BEP2D cell line and its malignant transformant, the BERP35T1 cell line. Our results demonstrated the distinctive methylation pattern for these tumor suppressor genes in radiation-induced malignant cells, as compared to their wild-type counterparts. Our study revealed epigenetic signatures for the characterization of radiation-mediated carcinogenesis and it may facilitate early diagnosis of patients at high risk for lung cancer.