DNA methylation and targeted sequencing of methyltransferases family genes in canine acute myeloid leukaemia, modelling human myeloid leukaemia.
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.
Oncohematology Laboratory, Department of Women's and Children's Health, University of Padova, Padova, Italy.
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I
Bronzini
Department of Comparative Biomedicine and Food Science, University of Padova, Padova, Italy.
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L
Aresu
Oncohematology Laboratory, Department of Women's and Children's Health, University of Padova, Padova, Italy.
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M
Paganin
Department of Cellular Biotechnology and Hematology, Sapienza University of Rome, Rome, Italy.
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L
Marchioretto
Department of Veterinary Science and Public Health, University of Milan, Milano, Italy.
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S
Comazzi
Department of Veterinary Medicine, University of Cambridge, Cambridge, UK.
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F
Cian
Department of Veterinary Sciences, University of Turin, Turin, Italy.
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F
Riondato
Centro Oncologico Veterinario, Sasso Marconi, Bologna, Italy.
L
L
Marconato
Department of Veterinary Science and Public Health, University of Milan, Milano, Italy.
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http://orcid.org/0000-0002-9882-2867
V
Martini
Oncohematology Laboratory, Department of Women's and Children's Health, University of Padova, Padova, Italy.
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G
Te Kronnie
D000818:Animals; D016022:Case-Control Studies; D019175:DNA Methylation / Q000235:genetics*; D015254:DNA Modification Methylases / Q000235:genetics*; D004195:Disease Models, Animal; D004283:Dog Diseases / Q000235:genetics*; D004285:Dogs; D005260:Female; D005434:Flow Cytometry / Q000662:veterinary; D020022:Genetic Predisposition to Disease / Q000235:genetics; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000662:veterinary*; D008297:Male
D015254:DNA Modification Methylases
DNA methylation; DNMT3 genes; Hematology; acute myeloid leukemia; hematopoietic tumor