title: Recurrent DNMT3A R882 mutations in Chinese patients with acute myeloid leukemia and myelodysplastic syndrome.
abstract: Somatic mutations of DNMT3A gene have recently been reported in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). We examined the entire coding sequences of DNMT3A gene by high-resolution melting analysis and sequencing in Chinese patients with myeloid malignancies. R882 mutations were found in 12/182 AML and in 4/51 MDS, but not in either 79 chronic myeloid leukemia (CML), or 57 myeloproliferative neoplasms (MPNs), or 4 chronic monomyelocytic leukemia. No other DNMT3A mutations were detected in all patients. R882 mutations were associated with old age and more frequently present in monoblastic leukemia (M4 and M5, 7/52) compared to other subtypes (5/130). Furthermore, 14/16 (86.6%) R882 mutations were observed in patients with normal karyotypes. The overall survival of mutated MDS patients was shorter than those without mutation (median 9 and 25 months, respectively). We conclude that DNMT3A R882 mutations are recurrent molecular aberrations in AML and MDS, and may be an adverse prognostic event in MDS.
authors: Department of Haematology, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China.
authors: Jiang
authors: J
authors: Lin
authors: Dong-ming
authors: DM
authors: Yao
authors: Jun
authors: J
authors: Qian
authors: Qin
authors: Q
authors: Chen
authors: Wei
authors: W
authors: Qian
authors: Yun
authors: Y
authors: Li
authors: Jing
authors: J
authors: Yang
authors: Cui-zhu
authors: CZ
authors: Wang
authors: Hai-yan
authors: HY
authors: Chai
authors: Zhen
authors: Z
authors: Qian
authors: Gao-fei
authors: GF
authors: Xiao
authors: Wen-rong
authors: WR
authors: Xu
mesh_terms: D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002681:China; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics*; D000090205:DNA Methyltransferase 3A; D004252:DNA Mutational Analysis; D006410:Hematopoiesis / Q000235:genetics; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics*; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics*; D009691:Nucleic Acid Denaturation; D016019:Survival Analysis
chemical_list: C000717967:DNMT3A protein, human; D050505:Mutant Proteins; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A