title: DFNA5 promoter methylation a marker for breast tumorigenesis.
abstract: BACKGROUND
  Identification of methylation markers that are sensitive and specific for breast cancer may improve early detection. We hypothesize that DFNA5 promoter methylation can be a valuable epigenetic biomarker, based upon strong indications for its role as tumor suppressor gene and its function in regulated cell death.
  
  
  RESULTS
  Statistically different levels of methylation were seen, with always very low levels in healthy breast reduction samples, very high levels in part of the adenocarcinoma samples and slightly increased levels in part of the normal tissue samples adjacent the tumor. One of the CpGs (CpG4) showed the best differentiation. A ROC curve for DFNA5 CpG4 methylation showed a sensitivity of 61.8% for the detection of breast cancer with a specificity of 100%.
  
  
  METHODS
  We performed methylation analysis on four CpGs in the DFNA5 promoter region by bisulfite pyrosequencing on 123 primary breast adenocarcinomas and 24 healthy breast reductions. For 16 primary tumors, corresponding histological normal tissue adjacent to the tumor was available.
  
  
  CONCLUSIONS
  We conclude that DFNA5 methylation shows strong potential as a biomarker for detection of breast cancer. Slightly increased methylation in histologically normal breast tissue surrounding the tumor suggests that it may be a good early detection marker.
authors.affiliation: Center of Medical Genetics, University of Antwerp and Antwerp University Hospital, Edegem B-2650, Belgium.|Center for Oncological Research, University of Antwerp and Antwerp University Hospital, Edegem B-2650, Belgium.
authors.forename: Lieselot
authors.initials: L
authors.lastname: Croes
authors.affiliation: Center of Medical Genetics, University of Antwerp and Antwerp University Hospital, Edegem B-2650, Belgium.|Center for Oncological Research, University of Antwerp and Antwerp University Hospital, Edegem B-2650, Belgium.
authors.forename: Ken Op
authors.initials: KO
authors.lastname: de Beeck
authors.affiliation: Center for Oncological Research, University of Antwerp and Antwerp University Hospital, Edegem B-2650, Belgium.
authors.forename: Patrick
authors.initials: P
authors.lastname: Pauwels
authors.affiliation: Laboratory of Protein Chemistry, Proteomics and Epigenetic Signaling (PPES), Antwerp B-2610, Belgium.
authors.forename: Wim
authors.initials: W
authors.lastname: Vanden Berghe
authors.affiliation: Center for Oncological Research, University of Antwerp and Antwerp University Hospital, Edegem B-2650, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: Peeters
authors.affiliation: Center of Medical Genetics, University of Antwerp and Antwerp University Hospital, Edegem B-2650, Belgium.|StatUa Center for Statistics, University of Antwerp, Antwerp B-2000, Belgium.
authors.forename: Erik
authors.initials: E
authors.lastname: Fransen
authors.affiliation: Center of Medical Genetics, University of Antwerp and Antwerp University Hospital, Edegem B-2650, Belgium.
authors.forename: Guy
authors.initials: G
authors.lastname: Van Camp
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D011401:Promoter Regions, Genetic; D012372:ROC Curve
chemical_list: D014408:Biomarkers, Tumor
keywords: DFNA5; DNA methylation; biomarker; breast cancer; detection