Panjarian Shoghag, Issa Jean-Pierre J
Coriell Institute Research Department, Coriell Institute for Medical Research, Camden, NJ 08103, USA.
Pharmaceuticals (Basel). 2021 Jun 29;14(7):628. doi: 10.3390/ph14070628.
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.
三阴性乳腺癌（TNBC）具有高度异质性、分子多样性，且具有高复发或转移倾向。临床上，由于缺乏激素受体（雌激素受体（ER）和孕激素受体（PR））以及HER2未过表达和/或扩增，TNBC仍是一种排除性诊断。DNA甲基化在乳腺癌致癌过程中起重要作用，与所有其他亚型相比，TNBC具有独特的DNA甲基化谱，其特征是显著的低甲基化和较低的甲基化增加。DNA甲基化由DNA甲基转移酶（DNMT）和DNA去甲基化酶（TET）的平衡调节。在此，我们综述了TET作为实体瘤中依赖于背景的肿瘤抑制基因和/或癌基因的作用，并讨论了目前对TET1致癌作用及其在TNBC中的治疗意义的理解。
