title: High methylation rate of LMX1A, NKX6-1, PAX1, PTPRR, SOX1, and ZNF582 genes in cervical adenocarcinoma.
abstract: OBJECTIVE
  This study aimed to investigate the status of DNA methylation of 6 genes, LMX1A, NKX6-1, PAX1, PTPRR, SOX1, and ZNF582, previously found from squamous cell carcinomas in adenocarcinomas (ACs) of the uterine cervix.
  
  
  METHODS
  We assessed the methylation status of these genes in 40 ACs, cervical scrapings from 23 ACs, and 67 normal control cervices by real-time quantitative methylation-specific polymerase chain reaction. The results were validated by bisulfite pyrosequencing.
  
  
  RESULTS
  The methylation levels of all the 6 genes in the ACs were significantly higher than those in normal cervical tissues, especially for PAX1, PTPRR, SOX1, and ZNF582. The odds ratios and 95% confidence intervals (CIs) of high methylation levels in PAX1, PTPRR, SOX1, and ZNF582 for the risk of developing an AC were 15.7 (95% CI, 7.0-40.6), 16.9 (95% CI, 7.6-43.0), 32.1 (95% CI, 12.1-124.3), and 25.4 (95% CI, 10.4-78.3), respectively (all P < 0.001). The methylation indices of PAX1, PTPRR, SOX1, and ZNF582 recovered from scrapings of ACs were significantly higher than in normal controls. The odds ratios of these indices for the risk of developing an AC in PAX1, PTPRR, SOX1, and ZNF582 were 6.2 (95% CI, 2.6-15.4), 12.1(95% CI, 3.8-46.4), 6.2 (95% CI, 2.6-15.8), and 20.6 (95% CI, 6.9-77.5), respectively (all P < 0.001).
  
  
  CONCLUSIONS
  Cervical ACs carry aberrantly high methylation rates of PAX1, PTPRR, SOX1, and ZNF582--commonly methylated in squamous cell carcinomas--which might help for AC screening.
authors.affiliation: *Department of Obstetrics and Gynecology, Tri-Service General Hospital; †Laboratory of Epigenetics and Cancer Stem Cells, and ‡Graduate Institute of Medical Sciences, National Defense Medical Center; and §Department of Obstetrics and Gynecology, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan, Republic of China.
authors.forename: Cheng-Chang
authors.initials: CC
authors.lastname: Chang
authors.forename: Rui-Lan
authors.initials: RL
authors.lastname: Huang
authors.forename: Hui-Chen
authors.initials: HC
authors.lastname: Wang
authors.forename: Yu-Ping
authors.initials: YP
authors.lastname: Liao
authors.forename: Mu-Hsien
authors.initials: MH
authors.lastname: Yu
authors.forename: Hung-Cheng
authors.initials: HC
authors.lastname: Lai
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D019175:DNA Methylation; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics; D060850:LIM-Homeodomain Proteins / Q000235:genetics; D051761:Paired Box Transcription Factors / Q000235:genetics; D054634:Receptor-Like Protein Tyrosine Phosphatases, Class 7 / Q000235:genetics; D055748:SOXB1 Transcription Factors / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D018398:Homeodomain Proteins; D051741:Kruppel-Like Transcription Factors; D060850:LIM-Homeodomain Proteins; C078021:LMX1A protein, human; C105201:NKX6-1 protein, human; D051761:Paired Box Transcription Factors; C490906:SOX1 protein, human; D055748:SOXB1 Transcription Factors; D014157:Transcription Factors; C577358:ZNF582 protein, human; C070835:PAX1 transcription factor; C513469:PTPRR protein, human; D054634:Receptor-Like Protein Tyrosine Phosphatases, Class 7