Oncotarget

Research Papers:

DFNA5 promoter methylation a marker for breast tumorigenesis

Lieselot Croes _, Ken Op de Beeck, Patrick Pauwels, Wim Vanden Berghe, Marc Peeters, Erik Fransen and Guy Van Camp

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Oncotarget. 2017; 8:31948-31958. https://doi.org/10.18632/oncotarget.16654

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Abstract

Lieselot Croes1,2, Ken Op de Beeck1,2, Patrick Pauwels2, Wim Vanden Berghe3, Marc Peeters2, Erik Fransen1,4, Guy Van Camp1

1Center of Medical Genetics, University of Antwerp and Antwerp University Hospital, Edegem B-2650, Belgium

2Center for Oncological Research, University of Antwerp and Antwerp University Hospital, Edegem B-2650, Belgium

3Laboratory of Protein Chemistry, Proteomics and Epigenetic Signaling (PPES), Antwerp B-2610, Belgium

4StatUa 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     Accepted: March 16, 2017     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.


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