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Whole-genome bisulfite sequencing of cell-free DNA identifies signature associated with metastatic breast cancer

Authors :
Christophe Legendre
Bodour Salhia
Rae Anne Martinez
Kyle N. Johnson
Winnie S. Liang
Gerald C. Gooden
Source :
Clinical Epigenetics
Publication Year :
2015

Abstract

Background A 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). Results Differential methylation analysis revealed ~5.0 × 106 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. Conclusions This 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. Electronic supplementary material The online version of this article (doi:10.1186/s13148-015-0135-8) contains supplementary material, which is available to authorized users.

Details

ISSN :
18687075
Volume :
7
Database :
OpenAIRE
Journal :
Clinical epigenetics
Accession number :
edsair.doi.dedup.....a447fe9b1cf0ecd7b440c0c91761aaec