Genome-wide DNA methylation pattern changes in basal-like breast cancer patients

Ten eleven translocation enzymes (TET1-3) convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), inducing DNA demethylation and gene regulation. They are often downregulated in cancer, yet the upstream cause of this event remains largely unknown. Here, we show increased TET1 expression in basal-like breast cancer (BLBC), specifically in tumors with low expression of immune markers and low infiltration by immune cells. Furthermore, we identify an anti-correlation between TET1 expression and NF-κB, a major immune regulatory family, in BLBC tissues. In vitro and in vivo, TET1 is downregulated in breast cells upon activation of NF-κB, through binding of p65 to its consensus sequence in the TET1 promoter. Moreover, we uncover genome-wide 5hmC changes related to TET1 regulation in BLBC. Finally, these findings are extended to other cancer types, including melanoma, lung and thyroid cancers. Collectively, our data suggest a novel mode of regulation for TET1, linking TETs and immunity, two major features of cancer. Genome-wide profiling of DNA methylation in 4 pairs of matched tumor and normal breast