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.
DNA methylation and targeted sequencing of methyltransferases family genes in canine acute myeloid leukaemia, modelling human myeloid leukaemia / I. Bronzini, L. Aresu, M. Paganin, L. Marchioretto, S. Comazzi, F. Cian, F. Riondato, L. Marconato, V. Martini, G. te Kronnie. - In: VETERINARY AND COMPARATIVE ONCOLOGY. - ISSN 1476-5810. - 15:3(2016 Sep), pp. 910-918.
|Titolo:||DNA methylation and targeted sequencing of methyltransferases family genes in canine acute myeloid leukaemia, modelling human myeloid leukaemia|
MARTINI, VALERIA (Penultimo)
|Parole Chiave:||Acute myeloid leukemia; DNA methylation; DNMT3 genes; Hematology; Hematopoietic tumor|
|Settore Scientifico Disciplinare:||Settore VET/03 - Patologia Generale e Anatomia Patologica Veterinaria|
|Data di pubblicazione:||set-2016|
|Data ahead of print / Data di stampa:||21-apr-2016|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1111/vco.12231|
|Appare nelle tipologie:||01 - Articolo su periodico|
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