The Roles of DNA Demethylases in Triple-Negative Breast Cancer

Triple-negative breast cancers (TNBCs) are very heterogenous, molecularly diverse, and are characterized by a high propensity to relapse or metastasize. Clinically, TNBC remains a diagnosis of exclusion by the lack of hormone receptors (Estrogen Receptor (ER) and Progesterone Receptor (PR)) as well as the absence of overexpression and/or amplification of HER2. DNA methylation plays an important role in breast cancer carcinogenesis and TNBCs have a distinct DNA methylation profile characterized by marked hypomethylation and lower gains of methylations compared to all other subtypes. DNA methylation is regulated by the balance of DNA methylases (DNMTs) and DNA demethylases (TETs). Here, we review the roles of TETs as context-dependent tumor-suppressor genes and/or oncogenes in solid tumors, and we discuss the current understandings of the oncogenic role of TET1 and its therapeutic implications in TNBCs.

Automated summary

Triple-negative breast cancers (TNBCs) are highly heterogeneous and molecularly diverse, with a distinct DNA methylation profile characterized by hypomethylation and lower gains of methylations compared to other subtypes. The balance between DNA methylases (DNMTs) and DNA demethylases (TETs) plays a crucial role in regulating DNA methylation in TNBCs.