DFNA5 Methylation: A Potential Biomarker for Breast Cancer?

There is a need for new biomarkers for early detection of breast cancer. DFNA5 promoter methylation has the potential to become such a new biomarker, because it has been demonstrated that DFNA5 is epigenetically inactivated in several types of cancer, including breast cancer. The aim of this study was to investigate DFNA5 promoter methylation as a potential molecular biomarker for breast cancer using pyrosequencing. In this study, we showed that the % of DFNA5 promotor methylation was significantly different between the 115 primary breast adenocarcinoma and the 17 histological normal breast tissues from breast reductions of non-cancerous patients (p = 8.8 10-16). In contrast, there was no difference in the DFNA5 promotor methylation between 13 paired samples of breast adenocarcinoma and histological normal tissues that were located adjacent to the tumour. Additionally, interesting associations between the % of DFNA5 promotor methylation and age (p = 0.026; R2 = 0.043) and HER2 amplification (p = 0.017; R2 = 0.118) were found. The DFNA5 promoter methylation results are interesting and promising. We believe that DFNA5 methylation might be a candidate to incorporate in a panel of markers to detect breast cancer. A possible explanation for the fact that there is no statistical significant difference in DFNA5 promoter methylation between breast adenocarcinoma and histological normal tissues at a distance of the tumour might be “field cancerisation” which is defined as the occurrence of genetic, epigenetic, and biochemical aberrations in structurally intact cells in histologically normal tissues adjacent to cancerous lesions. We believe that further research on DFNA5 methylation forms a strong opportunity. Furthermore, the observed associations with age and HER2 amplification are noteworthy. More research is needed to elucidate the cause of the association with these parameters, because this could lead to more insights into tumourigenesis, or a better molecular subclassification. Disclosure: All authors have declared no conflicts of interest.