title: Aberrant methylation of IL-12Rbeta2 gene in lung adenocarcinoma cells is associated with unfavorable prognosis.
abstract: 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.
authors.affiliation: Department of Thoracic Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Suzuki
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Iizasa
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nakajima
authors.forename: Rieko
authors.initials: R
authors.lastname: Kubo
authors.forename: Akira
authors.initials: A
authors.lastname: Iyoda
authors.forename: Kenzo
authors.initials: K
authors.lastname: Hiroshima
authors.forename: Yukio
authors.initials: Y
authors.lastname: Nakatani
authors.forename: Takehiko
authors.initials: T
authors.lastname: Fujisawa
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics; D019175:DNA Methylation; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D018664:Interleukin-12 / Q000235:genetics*; D008175:Lung Neoplasms / Q000235:genetics*; D011379:Prognosis; D016016:Proportional Hazards Models; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D014407:Tumor Cells, Cultured
chemical_list: D018664:Interleukin-12