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DNA methylation and targeted sequencing of methyltransferases family genes in canine acute myeloid leukaemia, modelling human myeloid leukaemia
Author(s) -
Bronzini I.,
Aresu L.,
Paganin M.,
Marchioretto L.,
Comazzi S.,
Cian F.,
Riondato F.,
Marconato L.,
Martini V.,
te Kronnie G.
Publication year - 2017
Publication title -
veterinary and comparative oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.864
H-Index - 34
eISSN - 1476-5829
pISSN - 1476-5810
DOI - 10.1111/vco.12231
Subject(s) - dna methylation , methylation , biology , methyltransferase , gene , epigenetics , dna , mutation , myeloid , cancer research , dna sequencing , genetics , dna methyltransferase , myeloid leukemia , microbiology and biotechnology , gene expression
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.