TET2
小结
TET2是抑癌基因，编码蛋白属于α-酮戊二酸和铁依赖性酶家族，参与将5-甲基胞嘧啶转化为5-羟甲基胞嘧啶。这种激活的DNA去甲基化有关的修饰对于细胞重编程和基因调控是重要的。在动物模型中，TTE2缺失与其他突变如JAK2和FLT3-ITD协同作用，以促进癌症进展，并能诱导基因组超甲基化并增加干细胞自我更新。TET2突变在血液系统恶性肿瘤中最常见。在具有克隆性造血作用而无明显的造血系统疾病的个体中也发现了TET2的单独突变。然而，这些患者随着年龄的增长会有较高风险发展为血液肿瘤。TET家族酶活性也会被IDH1和IDH2的特定突变所抑制，IDH1和IDH2会产生一种抑制性的辅因子，2-羟基戊二酸。WT1的突变也可能影响TET2作为相关的辅因子的功能。
TET2, a tumor suppressor and DNA demethylase, is frequently mutated in hematologic malignancies.TET2 belongs to a family of alpha-ketoglutarate and iron-dependent enzymes involved in converting 5-methylcytosine to 5-hydroxymethylcytosine. This modification is implicated in active DNA demethylation, a process that is important for cellular reprogramming and gene regulation. TET2 has been shown to function as a tumor suppressor with mutations leading to loss-of-function, particularly those affecting the C-terminal catalytic domain. In animal models, TET2 loss cooperates with other mutations such as JAK2 and FLT3-ITD mutations to promote cancer progression and can induce genomic hypermethylation and increase stem cell self-renewal. TET2 mutations are most often found in hematologic malignancies. Isolated mutations in TET2 have also been found in individuals with clonal hematopoiesis but with no apparent hematologic disease. However, these patients are at a higher risk of developing hematologic cancer with aging. TET family enzyme activity is also inhibited by specific mutations in IDH1 and IDH2 that produce an inhibitory co-factor, 2-hydroxyglutarate . Mutations in WT1 may also affect TET2 function as an associated co-factor.