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Vet Comp Oncol ; 15(3): 910-918, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27098563

RESUMO

Tumours shows aberrant DNA methylation patterns, being hypermethylated or hypomethylated compared with normal tissues. In human acute myeloid leukaemia (hAML) mutations in DNA methyltransferase (DNMT3A) are associated to a more aggressive tumour behaviour. As AML is lethal in dogs, we defined global DNA methylation content, and screened the C-terminal domain of DNMT3 family of genes for sequence variants in 39 canine acute myeloid leukaemia (cAML) cases. A heterogeneous pattern of DNA methylation was found among cAML samples, with subsets of cases being hypermethylated or hypomethylated compared with healthy controls; four recurrent single nucleotide variations (SNVs) were found in DNMT3L gene. Although SNVs were not directly correlated to whole genome DNA methylation levels, all hypomethylated cAML cases were homozygous for the deleterious mutation at p.Arg222Trp. This study contributes to understand genetic modifications of cAML, leading up to studies that will elucidate the role of methylome alterations in the pathogenesis of AML in dogs.


Assuntos
Metilação de DNA/genética , Metilases de Modificação do DNA/genética , Doenças do Cão/genética , Leucemia Mieloide Aguda/veterinária , Animais , Estudos de Casos e Controles , Modelos Animais de Doenças , Cães , Feminino , Citometria de Fluxo/veterinária , Predisposição Genética para Doença/genética , Leucemia Mieloide Aguda/genética , Masculino
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