title: Rare occurrence of DNMT3A mutations in myelodysplastic syndromes.
abstract: Gene mutations and epigenetic changes have been shown to play significant roles in the pathogenesis of myelodysplastic syndromes. Recently, mutations in DNMT3A were identified in 22.1% of patients with acute myeloid leukemia. In this study, we analyzed the frequency and clinical impact of DNMT3A mutations in a cohort of 193 patients with myelodysplastic syndromes. Mutations in DNMT3A were found in 2.6% of patients. The majority of mutations were heterozygous missense mutations affecting codon R882. Patients with DNMT3A mutations were found to have a higher rate of transformation to acute myeloid leukemia. When assessing the global methylation levels in patients with mutated versus unmutated DNMT3A and healthy controls no difference in global DNA methylation levels between the two groups was seen. Our data show that in patients with myelodysplastic syndromes, DNMT3A mutations occur at a low frequency and may be a risk factor for leukemia progression.
authors: Department of Hematology, Hannover Medical School, Hannover, Germany. thol.felicitas@mh-hannover.de
authors: Felicitas
authors: F
authors: Thol
authors: Claudia
authors: C
authors: Winschel
authors: Andrea
authors: A
authors: Lüdeking
authors: Haiyang
authors: H
authors: Yun
authors: Inna
authors: I
authors: Friesen
authors: Frederik
authors: F
authors: Damm
authors: Katharina
authors: K
authors: Wagner
authors: Jürgen
authors: J
authors: Krauter
authors: Michael
authors: M
authors: Heuser
authors: Arnold
authors: A
authors: Ganser
mesh_terms: D000293:Adolescent; D000328:Adult; D015331:Cohort Studies; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics*; D000090205:DNA Methyltransferase 3A; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D012307:Risk Factors
chemical_list: C000717967:DNMT3A protein, human; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A