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Clinical Epigenetics

, 7:100

First Online: 16 September 2015Received: 03 June 2015Accepted: 08 September 2015

Abstract

BackgroundA number of clinico-pathological criteria and molecular profiles have been used to stratify patients into high- and low-risk groups. Currently, there are still no effective methods to determine which patients harbor micrometastatic disease after standard breast cancer therapy and who will eventually develop local or distant recurrence. The purpose of our study was to identify circulating DNA methylation changes that can be used for prediction of metastatic breast cancer MBC.

ResultsDifferential methylation analysis revealed ~5.0 × 10 differentially methylated CpG loci in MBC compared with healthy individuals H or disease-free survivors DFS. In contrast, there was a strong degree of similarity between H and DFS. Overall, MBC demonstrated global hypomethylation and focal CpG island CPGI hypermethylation. Data analysis identified 21 novel hotspots, within CpG islands, that differed most dramatically in MBC compared with H or DFS.

ConclusionsThis unbiased analysis of cell-free cf DNA identified 21 DNA hypermethylation hotspots associated with MBC and demonstrated the ability to distinguish tumor-specific changes from normal-derived signals at the whole-genome level. This signature is a potential blood-based biomarker that could be advantageous at the time of surgery and-or after the completion of chemotherapy to indicate patients with micrometastatic disease who are at a high risk of recurrence and who could benefit from additional therapy.

AbbreviationscfDNAcell-free DNA

CPGICpG island

DFSdisease-free survivors

DMLdifferentially methylated loci

DMVdifferential methylation value

Hhealthy individuals

IGVIntegrated Genomic Viewer

KTBKomen Tissue Bank

MBCmetastatic breast cancer

MRDminimal residual disease

WGBSwhole-genome bisulfite sequencing

Christophe Legendre and Gerald C. Gooden contributed equally to this work.

Electronic supplementary materialThe online version of this article doi:10.1186-s13148-015-0135-8 contains supplementary material, which is available to authorized users.

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Author: Christophe Legendre - Gerald C. Gooden - Kyle Johnson - Rae Anne Martinez - Winnie S. Liang - Bodour Salhia

Source: https://link.springer.com/







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