DNA methylation and targeted sequencing of methyltransferases family genes in canine acute myeloid leukaemia,modelling human myeloid leukaemia |
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| Authors: | I Bronzini L Aresu M Paganin L Marchioretto S Comazzi F Cian F Riondato L Marconato V Martini G te Kronnie |
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| Institution: | 1. Oncohematology Laboratory, Department of Women's and Children's Health, University of Padova, Padova, Italy;2. Department of Comparative Biomedicine and Food Science, University of Padova, Padova, Italy;3. Department of Cellular Biotechnology and Hematology, Sapienza University of Rome, Rome, Italy;4. Department of Veterinary Science and Public Health, University of Milan, Milano, Italy;5. Department of Veterinary Medicine, University of Cambridge, Cambridge, UK;6. Department of Veterinary Sciences, University of Turin, Turin, Italy;7. Centro Oncologico Veterinario, Sasso Marconi, Bologna, Italy |
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| Abstract: | 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. |
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| Keywords: | acute myeloid leukemia DNA methylation DNMT3 genes Hematology hematopoietic tumor |
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