Dysregulated TET Family Genes and Aberrant 5mC Oxidation in Breast Cancer: Causes and Consequences

Simple Summary Both genetic and epigenetic mechanisms contribute to the pathogenesis of breast cancer. Since Tahiliani et al. identified TET1 as the first methyl-cytosine dioxygenase in 2009, accumulating evidence has shown that aberrant 5mC oxidation and dysregulated TET family genes are associated with diseases, including breast cancer. In this review we provide an overview on the diagnosis and prognosis values of aberrant 5mC oxidation in breast cancer and emphasize the causes and consequences of such epigenetic alterations. DNA methylation (5-methylcytosine, 5mC) was once viewed as a stable epigenetic modification until Rao and colleagues identified Ten-eleven translocation 1 (TET1) as the first 5mC dioxygenase in 2009. TET family genes (including TET1, TET2, and TET3) encode proteins that can catalyze 5mC oxidation and consequently modulate DNA methylation, not only regulating embryonic development and cellular differentiation, but also playing critical roles in various physiological and pathophysiological processes. Soon after the discovery of TET family 5mC dioxygenases, aberrant 5mC oxidation and dysregulation of TET family genes have been reported in breast cancer as well as other malignancies. The impacts of aberrant 5mC oxidation and dysregulated TET family genes on the different aspects (so-called cancer hallmarks) of breast cancer have also been extensively investigated in the past decade. In this review, we summarize current understanding of the causes and consequences of aberrant 5mC oxidation in the pathogenesis of breast cancer. The challenges and future perspectives of this field are also discussed.