title: Whole-genome bisulfite sequencing of cell-free DNA identifies signature associated with metastatic breast cancer.
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 × 10(6) 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.
authors.affiliation: Integrated Cancer Genomics Division, Translational Genomics Research Institute, 445 N Fifth Street, Phoenix, AZ USA.
authors.forename: Christophe
authors.initials: C
authors.lastname: Legendre
authors.affiliation: Integrated Cancer Genomics Division, Translational Genomics Research Institute, 445 N Fifth Street, Phoenix, AZ USA.
authors.forename: Gerald C
authors.initials: GC
authors.lastname: Gooden
authors.affiliation: Integrated Cancer Genomics Division, Translational Genomics Research Institute, 445 N Fifth Street, Phoenix, AZ USA.
authors.forename: Kyle
authors.initials: K
authors.lastname: Johnson
authors.affiliation: Integrated Cancer Genomics Division, Translational Genomics Research Institute, 445 N Fifth Street, Phoenix, AZ USA.
authors.forename: Rae Anne
authors.initials: RA
authors.lastname: Martinez
authors.affiliation: Integrated Cancer Genomics Division, Translational Genomics Research Institute, 445 N Fifth Street, Phoenix, AZ USA.
authors.forename: Winnie S
authors.initials: WS
authors.lastname: Liang
authors.affiliation: Integrated Cancer Genomics Division, Translational Genomics Research Institute, 445 N Fifth Street, Phoenix, AZ USA.
authors.forename: Bodour
authors.initials: B
authors.lastname: Salhia