BACKGROUND: Interleukin-12 receptor beta2 (IL-12Rbeta2) knock-out mice develop lung adenocarcinoma, and epigenetic silencing by CpG methylation leads to loss of this gene in B-cell malignancies. The aim of this study was to determine whether IL-12Rbeta2 methylation is a common feature in human lung cancer. METHODS: We examined mRNA expression of IL-12Rbeta2 in lung cancer cell lines, and normal bronchial, and tracheal epithelial cells using RT-PCR, and we examined the methylation status of IL-12Rbeta2 in primary lung cancers. RESULTS: Loss of expression was found in 10 of 13 (77%) NSCLC cell lines, and 2 of 5 (40%) SCLC cell lines compared with normal bronchial or tracheal cells. Treatment of 11 expression-negative cell lines with a demethylating agent restored expression in all cases. Aberrant methylation status of IL-12Rbeta2 gene was reversely concordant with its mRNA expression. IL-12Rbeta2 methylation was detected in 96 of 230 primary NSCLCs (42%) and 3 of 6 primary SCLCs (50%). IL-12Rbeta2 methylation correlated with poorer prognosis in lung adenocarcinomas (hazard ratio = 2.33, P = 0.0059). CONCLUSIONS: We conclude that epigenetic silencing of IL-12Rbeta2 is a frequent event in lung cancers. Aberrant methylation of this gene seems to be a useful predictor of long-term outcome for adenocarcinoma of the lung.
BACKGROUND:Interleukin-12 receptor beta2 (IL-12Rbeta2) knock-out mice develop lung adenocarcinoma, and epigenetic silencing by CpG methylation leads to loss of this gene in B-cell malignancies. The aim of this study was to determine whether IL-12Rbeta2 methylation is a common feature in humanlung cancer. METHODS: We examined mRNA expression of IL-12Rbeta2 in lung cancer cell lines, and normal bronchial, and tracheal epithelial cells using RT-PCR, and we examined the methylation status of IL-12Rbeta2 in primary lung cancers. RESULTS: Loss of expression was found in 10 of 13 (77%) NSCLC cell lines, and 2 of 5 (40%) SCLC cell lines compared with normal bronchial or tracheal cells. Treatment of 11 expression-negative cell lines with a demethylating agent restored expression in all cases. Aberrant methylation status of IL-12Rbeta2 gene was reversely concordant with its mRNA expression. IL-12Rbeta2 methylation was detected in 96 of 230 primary NSCLCs (42%) and 3 of 6 primary SCLCs (50%). IL-12Rbeta2 methylation correlated with poorer prognosis in lung adenocarcinomas (hazard ratio = 2.33, P = 0.0059). CONCLUSIONS: We conclude that epigenetic silencing of IL-12Rbeta2 is a frequent event in lung cancers. Aberrant methylation of this gene seems to be a useful predictor of long-term outcome for adenocarcinoma of the lung.
Authors: Kei Suzuki; Kyuichi Kadota; Camelia S Sima; Jun-ichi Nitadori; Valerie W Rusch; William D Travis; Michel Sadelain; Prasad S Adusumilli Journal: J Clin Oncol Date: 2012-12-26 Impact factor: 44.544