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DS CADAM Drafting V5-6R2018 SP3 x86. Software Description. CADAM Catia Modeling . The detection of a clearly heterogeneous distribution of epigenetic changes is not yet possible.

The experimental findings in metastatic cell lines are in sharp contrast to the *in situ* data in tumour samples, where a homogenous distribution of *de novo* CpG hypermethylation is associated with high-stage disease. Interestingly, profiling *in situ* of histological stages of breast cancer showed increased methylation in DNA derived from a more advanced stage, consistent with the proposed role of aberrant methylation in late tumour stages \[[@B42],[@B46]\]. In our study, we also investigated if methylation of *CDH13* had a tendency to increase in more advanced disease, as reported in the study of Cox *et al.*\[[@B41]\], but did not find such an association. In the light of the results we obtained for *CDH13*, a study focusing on the association between *CDH13* hypermethylation and the number of tumour-initiating cells is warranted in order to unravel the role of hypermethylation.

To conclude, we investigated a novel tumour suppressor gene (*CDH13*) and found that hypermethylation in primary breast tumours was associated with lower gene expression. This could be due to DNA methylation of the promoter of the *CDH13* gene, which leads to reduced gene expression. These results from the study of a comprehensive set of breast tumour samples can be considered valid for individual cases, but not for groups of patients.

Abbreviations
=============

(DMSO): Dimethyl sulfoxide; (DNMT): DNA methyltransferase; (IHC): Immunohistochemical analysis; (MSP): Methylation-specific polymerase chain reaction
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