title: [An update on epigenetic regulator gene mutations and pathogenesis of myelodysplastic syndromes].
abstract: The myelodysplastic syndrome (MDS) is a group of heterogeneous clonal disorders. So far, the etiology and pathogenesis of MDS is poorly understood. Recently, more and more epigenetic regulator gene such as TET2, ASXL1, EZH2, DNMT3A and UTX mutations were detected in patients with MDS: TET2 may convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (hmC). TET2 is the most frequently mutated gene in MDS known so far and it may act as tumor-suppressor gene. ASXL1 belongs to the enhancer of trithorax and Polycomb (ETP) gene group. MDS phenotypes may be caused not only by loss-of-function of ASXL1 but also by gain-of-function mutations, overexpression of this gene and so on. EZH2 is a kind of histone methyltransferase. EZH2 is frequently over-expressed in a wide variety of cancerous tissue types, which reveals it has oncogenic activity. While, defined mutations resulted in dysfunction of histone methyltransferase activity, suggesting that EZH2 acts as a tumor suppressor for myeloid malignancies. DNMT3A belongs to the DNA methyltransferases (DNMT) gene family. It may be correlated with abnormal methylation status in patients with MDS. UTX coding protein is a histone demethylase, and UTX can affect cell proliferation as well as cell fate decision. Inactivating UTX mutations are found in multiple cancer types recently. These gene mutations may play key roles in the pathogenesis of MDS, which are summarized in this review.
authors: Chinese Academy of Medical Sciences, Tianjin, China.
authors: Jie-Yu
authors: JY
authors: Wang
authors: Zhi-Jian
authors: ZJ
authors: Xiao
mesh_terms: D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics; D000090205:DNA Methyltransferase 3A; D004268:DNA-Binding Proteins / Q000235:genetics; D049308:Dioxygenases; D000071221:Enhancer of Zeste Homolog 2 Protein; D005809:Genes, Regulator; D016147:Genes, Tumor Suppressor; D056466:Histone Demethylases / Q000235:genetics; D006801:Humans; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000209:etiology* / Q000235:genetics* / Q000503:physiopathology; D009687:Nuclear Proteins / Q000235:genetics; D063151:Polycomb Repressive Complex 2 / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics
chemical_list: C473949:ASXL1 protein, human; D004268:DNA-Binding Proteins; C000717967:DNMT3A protein, human; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D049308:Dioxygenases; C541081:TET2 protein, human; D056466:Histone Demethylases; C523998:KDM6A protein, human; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2