title: Hypermethylation of testis derived transcript gene promoter significantly correlates with worse outcomes in glioblastoma patients.
abstract: BACKGROUND
  Glioblastoma is the most common and lethal cancer of the central nervous system. Global genomic hypomethylation and some CpG island hypermethylation are common hallmarks of these malignancies, but the effects of these methylation abnormalities on glioblastomas are still largely unclear. Methylation of the O6-methylguanine-DNA methyltransferase promoter is currently an only confirmed molecular predictor of better outcome in temozolomide treatment. To better understand the relationship between CpG island methylation status and patient outcome, this study launched DNA methylation profiles for thirty-three primary glioblastomas (pGBMs) and nine secondary glioblastomas (sGBMs) with the expectation to identify valuable prognostic and therapeutic targets.
  
  
  METHODS
  We evaluated the methylation status of testis derived transcript (TES) gene promoter by microarray analysis of glioblastomas and the prognostic value for TES methylation in the clinical outcome of pGBM patients. Significance analysis of microarrays was used for genes significantly differently methylated between 33 pGBM and nine sGBM. Survival curves were calculated according to the Kaplan-Meier method, and differences between curves were assessed using the log-rank test. Then, we treated glioblastoma cell lines (U87 and U251) with 5-aza-2-deoxycytidines (5-aza-dC) and detected cell biological behaviors.
  
  
  RESULTS
  Microarray data analysis identified TES promoter was hypermethylated in pGBMs compared with sGBMs (P < 0.05). Survival curves from the Kaplan-Meier method analysis revealed that the patients with TES hypermethylation had a short overall survival (P < 0.05). This abnormality is also confirmed in glioblastoma cell lines (U87 and U251). Treating these cells with 5-aza-dC released TES protein expression resulted in significant inhibition of cell growth (P = 0.013).
  
  
  CONCLUSIONS
  Hypermethylation of TES gene promoter highly correlated with worse outcome in pGBM patients. TES might represent a valuable prognostic marker for glioblastoma.
authors.affiliation: Department of Immunology, Capital Medical University, Beijing, China.
authors.forename: Li-jia
authors.initials: LJ
authors.lastname: Wang
authors.forename: Yu
authors.initials: Y
authors.lastname: Bai
authors.forename: Zhao-shi
authors.initials: ZS
authors.lastname: Bao
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.forename: Zhuo-hong
authors.initials: ZH
authors.lastname: Yan
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Quan-geng
authors.initials: QG
authors.lastname: Zhang
mesh_terms: D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003598:Cytoskeletal Proteins / Q000235:genetics*; D019175:DNA Methylation; D000077209:Decitabine; D005909:Glioblastoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D006801:Humans; D060588:LIM Domain Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic; D016601:RNA-Binding Proteins; D016896:Treatment Outcome
chemical_list: D003598:Cytoskeletal Proteins; D060588:LIM Domain Proteins; D016601:RNA-Binding Proteins; C429688:TES protein, human; D000077209:Decitabine; D001374:Azacitidine