title: Methylomic analysis identifies frequent DNA methylation of zinc finger protein 582 (ZNF582) in cervical neoplasms.
abstract: BACKGROUND
  Despite of the trend that the application of DNA methylation as a biomarker for cancer detection is promising, clinically applicable genes are few. Therefore, we looked for novel hypermethylated genes for cervical cancer screening.
  
  
  RESULTS
  At the discovery phase, we analyzed the methylation profiles of human cervical carcinomas and normal cervixes by methylated DNA immunoprecipitation coupled to promoter tiling arrays (MeDIP-on-chip). Methylation-specific PCR (MSP), quantitative MSP and bisulfite sequencing were used to verify the methylation status in cancer tissues and cervical scrapings from patients with different severities. Immunohistochemical staining of a cervical tissue microarray was used to confirm protein expression. We narrowed to three candidate genes: DBC1, PDE8B, and ZNF582; their methylation frequencies in tumors were 93%, 29%, and 100%, respectively. At the pre-validation phase, the methylation frequency of DBC1 and ZNF582 in cervical scraping correlated significantly with disease severity in an independent cohort (n = 330, both P<0.001). For the detection of cervical intraepithelial neoplasia 3 (CIN3) and worse, the area under the receiver operating characteristic curve (AUC) of ZNF582 was 0.82 (95% confidence interval= 0.76-0.87).
  
  
  CONCLUSIONS
  Our study shows ZNF582 is frequently methylated in CIN3 and worse lesions, and it is demonstrated as a potential biomarker for the molecular screening of cervical cancer.
authors: Department of Obstetrics and Gynecology, Tri-Service General Hospital, Taipei, Taiwan.
authors: Rui-Lan
authors: RL
authors: Huang
authors: Cheng-Chang
authors: CC
authors: Chang
authors: Po-Hsuan
authors: PH
authors: Su
authors: Yu-Chih
authors: YC
authors: Chen
authors: Yu-Ping
authors: YP
authors: Liao
authors: Hui-Chen
authors: HC
authors: Wang
authors: Yi-Te
authors: YT
authors: Yo
authors: Tai-Kuang
authors: TK
authors: Chao
authors: Hsuan-Cheng
authors: HC
authors: Huang
authors: Ching-Yu
authors: CY
authors: Lin
authors: Tang-Yuan
authors: TY
authors: Chu
authors: Hung-Cheng
authors: HC
authors: Lai
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000096:biosynthesis / Q000235:genetics; D015415:Biomarkers / Q000378:metabolism; D018797:Cell Cycle Proteins; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000096:biosynthesis* / Q000235:genetics*; D009419:Nerve Tissue Proteins; D016133:Polymerase Chain Reaction / Q000379:methods; D011401:Promoter Regions, Genetic; D012372:ROC Curve; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis / Q000235:genetics; D002583:Uterine Cervical Neoplasms / Q000378:metabolism*; D016335:Zinc Fingers
chemical_list: C112308:BRINP1 protein, human; D015415:Biomarkers; D018797:Cell Cycle Proteins; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; D025521:Tumor Suppressor Proteins; C577358:ZNF582 protein, human; D015105:3',5'-Cyclic-AMP Phosphodiesterases; C468781:PDE8B protein, human