The role of TET family proteins and 5-hydroxymethylcytosine in human tumors.

Tumorigenesis correlates with hypermethylation of tumor suppressors and hypomethylation of oncogenes. DNA methyltransferases (DNMTs) catalyze DNA methylation, and mutations and aberrant expression in DNMT genes are found in multiple human tumors. The discovery of the DNA demethylation function of TET proteins has opened up new avenues for the study of DNA methylation regulation. TET proteins regulate the DNA demethylation pathway through oxidizing 5-mC into 5-hmC, 5-fC, and 5-aC. TET genes have been reported to be frequently mutated in hematopoietic malignancies and are associated with the malignant transformation of cells. Loss-of-function mutations in TET genes have not been reported in human solid tumors. However, 5-hmC has been found to be reduced in various solid tumors, indicating that TET genes may contribute to cellular transformation via regulation of DNA demethylation. As a new epigenetic modification, 5-hmC may be a useful biomarker for the diagnosis of cancers. To better understand the roles of TET and 5-hmC in tumors, the biological functions of TET and 5-hmC should be studied further.