<i>DFNA5</i>promoter methylation a marker for breast tumorigenesis

Abstract

// Lieselot Croes 1, 2 , Ken Op de Beeck 1, 2 , Patrick Pauwels 2 , Wim Vanden Berghe 3 , Marc Peeters 2 , Erik Fransen 1, 4 , Guy Van Camp 1 1 Center of Medical Genetics, University of Antwerp and Antwerp University Hospital, Edegem B-2650, Belgium 2 Center for Oncological Research, University of Antwerp and Antwerp University Hospital, Edegem B-2650, Belgium 3 Laboratory of Protein Chemistry, Proteomics and Epigenetic Signaling (PPES), Antwerp B-2610, Belgium 4 StatUa Center for Statistics, University of Antwerp, Antwerp B-2000, Belgium Correspondence to: Lieselot Croes, email: lieselot.croes@uantwerpen.be Keywords: DFNA5, breast cancer, DNA methylation, biomarker, detection Received: November 15, 2016&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Accepted: March 16, 2017&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Published: March 29, 2017 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%. Materials and 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.