Global DNA hypomethylation coupled to repressive chromatin domain formation and gene silencing in breast cancer

While genetic mutation is a hallmark of cancer, many cancers also acquire epigenetic alterations during tumorigenesis including aberrant DNA hypermethylation of tumor suppressors, as well as changes in chromatin modifications as caused by genetic mutations of the chromatin-modifying machinery. However, the extent of epigenetic alterations in cancer cells has not been fully characterized. Here, we describe complete methylome maps at single nucleotide resolution of a low-passage breast cancer cell line and primary human mammary epithelial cells. We find widespread DNA hypomethylation in the cancer cell, primarily at partially methylated domains (PMDs) in normal breast cells. Unexpectedly, genes within these…

• NS
  National Science Foundation

  Awards: NSF-CCF-1115206, 1115206
• HH
  Howard Hughes Medical Institute
• GA
  Gordon and Betty Moore Foundation
• MK
  Mary K. Chapman Foundation
• LI
  Ludwig Institute for Cancer Research
• NI
  National Institutes of Health