TET2 (D6B9Y) Rabbit mAb #18950

Methylation of DNA at cytosine residues is a heritable, epigenetic modification that is critical for proper regulation of gene expression, genomic imprinting, and mammalian development (1,2). 5-methylcytosine is a repressive epigenetic mark established de novo by two enzymes, DNMT3a and DNMT3b, and is maintained by DNMT1 (3, 4). 5-methylcytosine was originally thought to be passively depleted during DNA replication. However, subsequent studies have shown that Ten-Eleven Translocation (TET) proteins TET1, TET2, and TET3 can catalyze the oxidation of methylated cytosine to 5-hydroxymethylcytosine (5-hmC) (5). Additionally, TET proteins can further oxidize 5-hmC to form 5-formylcytosine (5-fC) and 5-carboxylcytosine (5-caC), both of which are excised by thymine-DNA glycosylase (TDG), effectively linking cytosine oxidation to the base excision repair pathway and supporting active cytosine demethylation (6,7). TET2 is the most frequently mutated gene in myeloid dysplastic syndrome (MDS), a dysplasia of myeloid, megakaryocytic, and/or erythroid cell lineages, of which 30% progress to acute myeloid leukemia (AML) (8, 9). It is also mutated in diffuse large B-cell lymphoma (10). TET2 protein expression is often reduced in solid tumors such as prostate cancer, melanoma, and oral squamous cell carcinoma (11-13).